Cursul nr 7Cursul nr 7Dezvoltarea sistemului locomotor Dezvoltarea sistemului locomotor (I). Dezvoltarea organului axial. (I). Dezvoltarea organului axial.

Derivatele mezoblastului Derivatele mezoblastului notocordal. organului axial. notocordal. organului axial.

Derivatele mezoblastului paraxial. Derivatele mezoblastului paraxial. Metameria somitică primară. Metameria somitică primară.

Metameria secundară. Metameria secundară.

SSoarta somitelor occipitaleoarta somitelor occipitale Conf univ. Dr. Gogulescvu NicolaeConf univ. Dr. Gogulescvu Nicolae

As. univ. Dr. Gogulescu Bogdan AdrianAs. univ. Dr. Gogulescu Bogdan Adrian

Saptamana 6Saptamana 6 CordCord::

4 “camere”4 “camere” Bataile inimii sunt detectabileBataile inimii sunt detectabile

StomacStomac: forma finala : forma finala TesticoleleTesticolele si si ovareleovarele incep sa incep sa

apara apara Schetetul primitivSchetetul primitiv in formare in formare

Inchiderea cerculuiInchiderea cercului

Sfera corialaSfera coriala

Placenta de la Placenta de la patru patru

saptamani la saptamani la patru lunipatru luni

PlacentaPlacenta4 x 44 x 4

Placenta 4 Placenta 4 => 4=> 4

Cartoful Cartoful fierbintefierbinte

Ana - FizioAna - Fizio

F.P.F.P.

Dezvoltarea sistemului locomotor (I). Dezvoltarea sistemului locomotor (I).

Mugurii membrelorMugurii membrelor

Dezvoltarea organului axial. Dezvoltarea organului axial.

Sectiune sagitala in embrionul Sectiune sagitala in embrionul de pasarede pasare

Fate map of the quail bud Fate map of the quail bud represented on a sagittal represented on a sagittal section of a 25-27ss chick or section of a 25-27ss chick or quail embryo. The superficial quail embryo. The superficial cells of the tail bud are fated cells of the tail bud are fated to form the neural tube by the to form the neural tube by the secondary neurulation secondary neurulation process. Ventrally, the cordo-process. Ventrally, the cordo-neural-hinge (CNH) prolongs neural-hinge (CNH) prolongs the notochord and floor plate the notochord and floor plate deposited during Hensen´s deposited during Hensen´s node (HN) regression. CNH node (HN) regression. CNH can be assimilated to HN. It is can be assimilated to HN. It is located rostral to the remnant located rostral to the remnant of the primitive streak that is of the primitive streak that is at the origin of the paraxial at the origin of the paraxial mesoderm of the posterior mesoderm of the posterior region of the body.region of the body.

Miscarea cranio-caudala a Miscarea cranio-caudala a nodului Hensennodului Hensen

Schematic representation Schematic representation of the rostro-caudal of the rostro-caudal movement of Hensen’s nodemovement of Hensen’s node

(HN). (A) Hensen´s node (HN). (A) Hensen´s node cells (red) bisect the cells (red) bisect the superficial layer of the sinus superficial layer of the sinus rhomboidalisrhomboidalis

(blue) which will become (blue) which will become the alar plates of the spinal the alar plates of the spinal cord. (B) Later on, the bulk cord. (B) Later on, the bulk ofof

Hensen’s node (1) becomes Hensen’s node (1) becomes segregated into three segregated into three layers: the floor plate, the layers: the floor plate, the notochordnotochord

and the dorsal endoderm and the dorsal endoderm (2).(2).

NICOLE M. LE DOUARIN – Early neurogenesis in Amniote vertebrates - J. Dev. Biol. 45: 373-378 (2001)

NeurulatiaNeurulatia Neurulatia Neurulatia se produce din ziua 14 pâna în ziua 30 de gestatie se produce din ziua 14 pâna în ziua 30 de gestatie

si consta în formarea si închiderea tubului neural, care si consta în formarea si închiderea tubului neural, care anterior plutea sub forma de placa neurala în lichidul amniotic. anterior plutea sub forma de placa neurala în lichidul amniotic. În saptamâna a 3-a placa neurala începe sa se largeasca si sa În saptamâna a 3-a placa neurala începe sa se largeasca si sa se invagineze înspre mezoderm si endoderm, pentru a forma se invagineze înspre mezoderm si endoderm, pentru a forma tubul neural. Defectele de neurulatie determina disrafiile tubul neural. Defectele de neurulatie determina disrafiile (anencefalie, encefalocel, meningocel, spina bifida).(anencefalie, encefalocel, meningocel, spina bifida).

Din zilele 25-30 de gestatie pâna în zilele 80-90 urmeaza Din zilele 25-30 de gestatie pâna în zilele 80-90 urmeaza faza faza de formare a emisferelor cerebrale de formare a emisferelor cerebrale (prozencefalizarea)(prozencefalizarea). . Înainte ca partea caudala sa fie deplin dezvoltata, partea Înainte ca partea caudala sa fie deplin dezvoltata, partea anterioara a primei somite cervicale începe sa se evagineze si anterioara a primei somite cervicale începe sa se evagineze si sa formeze flexiuni si cavitati, fiecare cu anumite semnificatii sa formeze flexiuni si cavitati, fiecare cu anumite semnificatii în dezvoltarea ulterioara. Initial se produc 3 evaginari: în dezvoltarea ulterioara. Initial se produc 3 evaginari: prozencefalul (creierul anterior), mezencefalul (creierul prozencefalul (creierul anterior), mezencefalul (creierul mijlociu), si rombencefalul (creierul posterior). Cu timpul, pe mijlociu), si rombencefalul (creierul posterior). Cu timpul, pe partile laterale ale prozencefalului apar alte 2 evaginari - partile laterale ale prozencefalului apar alte 2 evaginari - veziculele optice (se vor dezvolta nervii optici si o parte din veziculele optice (se vor dezvolta nervii optici si o parte din globii oculari). În ziua 36, prozencefalul se divide în diencefal globii oculari). În ziua 36, prozencefalul se divide în diencefal (posterior) si anterior in 2 vezicule telencefalice, care ulterior (posterior) si anterior in 2 vezicule telencefalice, care ulterior devin cele 2 emisfere cerebrale. Simultan se formeaza si devin cele 2 emisfere cerebrale. Simultan se formeaza si cavitatile telencefalice, care pe parcurs formeaza ventriculii cavitatile telencefalice, care pe parcurs formeaza ventriculii cerebrali. Odata cu divizarea creierului anterior cerebrali. Odata cu divizarea creierului anterior (prozencefalul), se divide si cel posterior (rombencefalul in (prozencefalul), se divide si cel posterior (rombencefalul in doua structuri: anterior viitoarea punte si cerebelul si doua structuri: anterior viitoarea punte si cerebelul si posterior - viitorul bulb si începutul maduvei spinarii. posterior - viitorul bulb si începutul maduvei spinarii. Cavitatile corespunzatoare devine ventriculul IV. Mezencefalul Cavitatile corespunzatoare devine ventriculul IV. Mezencefalul ramâne neschimbat, din el dezvoltându-se pedunculii cerebrali ramâne neschimbat, din el dezvoltându-se pedunculii cerebrali si lama cvadrigeminala. Cresterea si dezvoltarea continua si si lama cvadrigeminala. Cresterea si dezvoltarea continua si spre luna a 3-a. Concomitent, coarda spinala se extinde spre luna a 3-a. Concomitent, coarda spinala se extinde caudal, odata cu dezvoltarea coloanei vertebrale. Agresiunile caudal, odata cu dezvoltarea coloanei vertebrale. Agresiunile de orice tip sau perturbarea acestei importante etape dede orice tip sau perturbarea acestei importante etape de

Fate map of the posterior region of the Fate map of the posterior region of the embryo at 6ss. (A) In situ hybridization of embryo at 6ss. (A) In situ hybridization of a 6ss embryo with a Sox2 probe. At the a 6ss embryo with a Sox2 probe. At the level of the sinus rhomboidalis, the neural level of the sinus rhomboidalis, the neural ectoderm, as with the rest of the neural ectoderm, as with the rest of the neural plate, expresses Sox2. Note that the floor plate, expresses Sox2. Note that the floor plate, the node and the primitive streak plate, the node and the primitive streak are Sox2-negative. are Sox2-negative.

(B) The neural ectoderm (blue). Note the (B) The neural ectoderm (blue). Note the similarity between the Sox2-positive area similarity between the Sox2-positive area in (A) and the region of the sinus in (A) and the region of the sinus rhomboidalis destined to form the neural rhomboidalis destined to form the neural tube (NT) as revealed by the quail-chick tube (NT) as revealed by the quail-chick chimera system. In red, the notochord and chimera system. In red, the notochord and floor plate (No + FP) and the node (HN). floor plate (No + FP) and the node (HN). In yellow, the primitive streak. In yellow, the primitive streak.

(C) Transverse section at the thoracic (C) Transverse section at the thoracic level in an E3 (embryonic day 3) chick level in an E3 (embryonic day 3) chick embryo, showing the distribution of the embryo, showing the distribution of the areas labelled in B. The derivatives of areas labelled in B. The derivatives of Hensen’s node are the floor plate, the Hensen’s node are the floor plate, the notochod and the underlying dorsal notochod and the underlying dorsal endoderm (DE). endoderm (DE).

(D) Replacement of Hensen’s node in a (D) Replacement of Hensen’s node in a chick embryo by its quail counterpart chick embryo by its quail counterpart results in the labelling of midline cells results in the labelling of midline cells (red) from the level of somite 20 down to (red) from the level of somite 20 down to the caudal end of the spinal cord. The the caudal end of the spinal cord. The neural tube itself is derived from the neural tube itself is derived from the caudal extension of the neural ectoderm caudal extension of the neural ectoderm of the sinus rhomboidalis. BP, brachial of the sinus rhomboidalis. BP, brachial plexus; Lu P; lumbar plexus; s6, somite 6; plexus; Lu P; lumbar plexus; s6, somite 6; Th N, thoracic neural tubeTh N, thoracic neural tube

Experiment demonstrating that floor plate and neural tube Experiment demonstrating that floor plate and neural tube development does not depend upon an induction arising from the development does not depend upon an induction arising from the notochord. 1 At 6ss, the node region (red) of a chick embryo is notochord. 1 At 6ss, the node region (red) of a chick embryo is replaced by the same territory coming from a stage matched quail replaced by the same territory coming from a stage matched quail (left insert). At 22ss, the chick embryo carries a floor plate and a (left insert). At 22ss, the chick embryo carries a floor plate and a notochord (No) of quail origin from the level of somite 20 notochord (No) of quail origin from the level of somite 20 caudalwards. Excision of the notochord from this chimeric neural caudalwards. Excision of the notochord from this chimeric neural tube is carried out by using pancreatic enzymes. The notochord tube is carried out by using pancreatic enzymes. The notochord is removed while the floor plate remains in place in most of the is removed while the floor plate remains in place in most of the neural tube subjected to the operation (the floor plate here in red neural tube subjected to the operation (the floor plate here in red is HNF3 ßpositive, not shown). However, posteriorly, where is HNF3 ßpositive, not shown). However, posteriorly, where notochord and floor plate are fused in a single cell cord, the notochord and floor plate are fused in a single cell cord, the presumptive floor plate material is also removed and the neural presumptive floor plate material is also removed and the neural tube remains open ventrally (see (2) insert E2). After back tube remains open ventrally (see (2) insert E2). After back grafting, the spinal cord develops normally with a quail floor plate grafting, the spinal cord develops normally with a quail floor plate (QFP). 2 (A) In the absence of the notochord, quail cells are (QFP). 2 (A) In the absence of the notochord, quail cells are revealed with the QCPN monoclonal antibody (see Teillet et al., revealed with the QCPN monoclonal antibody (see Teillet et al., 1998). (B) The floor plate expresses Shh. (C) In contrast, in the 1998). (B) The floor plate expresses Shh. (C) In contrast, in the region of the tube devoid of floor plate, the neural tube develops region of the tube devoid of floor plate, the neural tube develops without the ventral horn and (D) does not show Shh expression without the ventral horn and (D) does not show Shh expression En, Embryonic day n. En, Embryonic day n.

Heterogenitatea nodului Heterogenitatea nodului HensenHensen

Heterogeneity in Hensen’s Heterogeneity in Hensen’s node at 6ss. Sagittal section node at 6ss. Sagittal section of the node and anterior of the node and anterior primitive streak (PS) primitive streak (PS) hybridized with HNF3 ß hybridized with HNF3 ß (yellow) and ch-Tbx6L (blue) (yellow) and ch-Tbx6L (blue) (caudal is to the right). Three (caudal is to the right). Three regions can be distinguished regions can be distinguished in the node region: zone a in the node region: zone a where notochord (No) and where notochord (No) and floor plate (FP) are closely floor plate (FP) are closely apposed but separated by a apposed but separated by a basement membrane; zone b basement membrane; zone b where this process is in where this process is in progress and zone c where progress and zone c where the HNF3ß + cells are the HNF3ß + cells are randomly arranged. The PS randomly arranged. The PS cells are ch-TbxL6+ and in cells are ch-TbxL6+ and in continuity with the node continuity with the node material. NE, neuroepithelium material. NE, neuroepithelium posterior to the median pitposterior to the median pit

Consequences of excision of Zone c of Hensen’s node. (A) Consequences of excision of Zone c of Hensen’s node. (A) Ventral view of the sinus rhomboidalis following in situ Ventral view of the sinus rhomboidalis following in situ hybridization with an HNF3ßhybridization with an HNF3ßprobe. The node is seen with the 3 a,b and c anteroposterior probe. The node is seen with the 3 a,b and c anteroposterior areas. Rostrally, HNF3ß labels the notochord. (B,C) Zone c areas. Rostrally, HNF3ß labels the notochord. (B,C) Zone c has been removed at E1.5. (D) Ventral view of an operated has been removed at E1.5. (D) Ventral view of an operated embryo one day after zone c excision. The caudal extension embryo one day after zone c excision. The caudal extension of the notochord (No) is stopped. Notochord forms a mass of the notochord (No) is stopped. Notochord forms a mass rostral to the excision site. Posteriorly, the neural tube (NT) rostral to the excision site. Posteriorly, the neural tube (NT) forms in the absence of midline cells. (E) Section of the forms in the absence of midline cells. (E) Section of the neural tube as shown in D hybridized with a Pax3 probeneural tube as shown in D hybridized with a Pax3 probe

De la “mic” la De la “mic” la “mare”“mare”

Formarea regiunii Formarea regiunii cefalicecefalice

Saptamana 4Saptamana 4

Invadarea creerului de Invadarea creerului de sangesange

Creer si maduva spinariiCreer si maduva spinarii

S.N.C. la 49 zileS.N.C. la 49 zile

Derivatele mezoblastului notocordal. Derivatele mezoblastului notocordal.

Dezvoltarea tubului Dezvoltarea tubului neuralneural

Tubul neural si somiteleTubul neural si somitele

Derivatele organului axial. Derivatele organului axial.

Derivatele mezoblastului paraxial. Derivatele mezoblastului paraxial.

Metameria somitică primarăMetameria somitică primară

Differentiation of Somites Into Differentiation of Somites Into Myotomes, Sclerotomes, and Myotomes, Sclerotomes, and

DermatomesDermatomes

22

Dermatoame la embrionDermatoame la embrion

Progressive Stages In Progressive Stages In Formation of Vertebral Formation of Vertebral

Column, Dermatomes, and Column, Dermatomes, and MyotomesMyotomes

22

DermatoameDermatoame A A dermatomedermatome is an area of  is an area of skinskin that is mainly supplied  that is mainly supplied

by a single by a single spinal nervespinal nerve. There are eight . There are eight cervical nervescervical nerves (C1 being an exception with no dermatome), twelve  (C1 being an exception with no dermatome), twelve thoracic nervesthoracic nerves, five , five lumbar nerveslumbar nerves and five  and five sacral nervessacral nerves. Each of these nerves relays sensation . Each of these nerves relays sensation (including pain) from a particular region of skin to the (including pain) from a particular region of skin to the brainbrain. .

Along the Along the thoraxthorax and  and abdomenabdomen the dermatomes are like  the dermatomes are like a stack of discs forming a human, each supplied by a a stack of discs forming a human, each supplied by a different spinal nerve. Along the arms and the legs, the different spinal nerve. Along the arms and the legs, the pattern is different: the dermatomes run longitudinally pattern is different: the dermatomes run longitudinally along the limbs. Although the general pattern is similar along the limbs. Although the general pattern is similar in all people, the precise areas of innervation are as in all people, the precise areas of innervation are as unique to an individual as fingerprints.unique to an individual as fingerprints.

A similar area innervated by A similar area innervated by peripheral nervesperipheral nerves is called  is called a a peripheral nerve fieldperipheral nerve field..

DermatoameDermatoame

Metameria Metameria secundarăsecundară

C2 - posterior half of the skull capC2 - posterior half of the skull cap C3 - area correlating to a high C3 - area correlating to a high

turtle neck shirtturtle neck shirt C4 - area correlating to a low-collar C4 - area correlating to a low-collar

shirtshirt C6 - (radial nerve) 1st digit (thumb)C6 - (radial nerve) 1st digit (thumb) C7 - (median nerve) 2nd and 3rd C7 - (median nerve) 2nd and 3rd

digitdigit C8 - (ulnar nerve) 4th and 5th digit C8 - (ulnar nerve) 4th and 5th digit

and medial-posterior aspect of armand medial-posterior aspect of arm T4 - nipples.T4 - nipples. T5 - Inframammary fold.T5 - Inframammary fold. T6/T7 - xiphoid process.T6/T7 - xiphoid process. T10 - umbilicus (important for early T10 - umbilicus (important for early

appendicitis pain)appendicitis pain) T12 - pubic bone area.T12 - pubic bone area. L1 - inguinal ligamentL1 - inguinal ligament L4 - includes the knee capsL4 - includes the knee caps S2/S3 - genitalia S2/S3 - genitalia

..

SSoarta oarta somitelor somitelor occipitaleoccipitale

Saptamana 10Saptamana 10

Saptamana Saptamana 1212

SaptamSaptamana 16ana 16

Saptamana 20Saptamana 20

23 saptamani23 saptamani

SaptamaSaptamana 24na 24

Saptamana 28Saptamana 28

Saptamana 36Saptamana 36

Saptamana 40Saptamana 40