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Molecular Embryology



                       By:
        Dr. Khaled El Masry
    Assistant Lecturer of Human Anatomy &
                   Embryology
Mansoura Faculty of Medicine, Mansoura University,
               Mansoura , Egypt.
                       2013
Molecular Regulation of
        Cardiac
     Development
BMP 2, 4 + Inhibitors of WNT genes (In Endoderm & Lateral Plate
Mesoderm )



             Stimulate Production of Signals from
                 Anterior Cranial Endoderm
                                  Expre
                                     ss
                         NKX 2.5
                                            Specify Cardiogenic
                                             Field in Overlying
                                                Mesoderm.
                                               Role in Cardiac
                                                    Septation.
                              Role in Conducting System Development.

       TBX-5 ( another                    Expressed later than NKX
    transcriptional factor)               2.5
       contain T- Box.

                                       Role in Cardiac
                                       Septation
Molecular Regulation of
        SomitE
    Differentiation
Limb & body wall
                         Epaxial muscles
                                    Activate Myogenin & MRF-5        muscles
WNT proteins                  MYF-5                                               MYOD
 ( from Neural Tube)                                   Myotubes &
                                                       Myofibrils



                              DM                    Midpart
                                                           NT-3 (from Neural
                                                                          Tube)


                       VM            SHH            Dermis


                                                                                  D
                   Scleroto
                            me
                                           PAX 1
    Initiate cascade of cartilage & bone forming genes
                                                                 Vertebral
                                                                 formation
                                                                                  L
    BY:
                Interaction ( ) BMP-4 ( from lateral plate mesoderm) & WNT proteins ( from
Dr. Khaled El   Epidermis)
                          WNT proteins                 PAX 3   Specify Dermomyotome Region of Somites
   Masry                 ( from Neural Tube)
Molecular Regulation of
          Gut
     Development
Differentiation of different regions of gut & its derivatives is dependent
                                    upon


Reciprocal interaction ( ) Endoderm of GUT & Surrounding Splanchnic
Mesoderm.
                                SHH ( Expressed throughout gut
                                      endoderm)
                                    Induce expression

                                HOX genes in
                                  Mesoderm
                                   Once expressed & Mesoderm specified by
                                   HOX genes
        Mesoderm instruct Endoderm to form various regions of
        Midgut & Hindgut




Similar Interactions are responsible for Partitioning of
Foregut.
Molecular Regulation of
        LIVER
     Development
All Foregut Endoderm has the ability to express liver-specific genes & to
differentiate into Liver tissue
                                     But
                This expression is blocked by factors produced from
               surrounding tissues including: Ectoderm, non- cardiac
                              mesoderm & Notochord.
                     Liver Development occurs
                               when:
     Cardiac Mesoderm            FGF4              Block the inhibitory signals in
                                                   prospective hepatic Region




This process is partially                             Cells differentiate into
regulated by HNF 3,4                                hepatocytes & Biliary cell
(Hepatocyte Nuclear                                           lineage
Transcription Factors 3 & 4 )
Molecular Regulation of
       Pancreas
     Development
Notochord                     FGF &                 Suppress SHH ( in
                                      Activin               gut endoderm that
                                                                 form the will
                                                                     pancreas



                                                       Upregulate PDX genes
                                                       ( Pancreatic & Duodenal
                                                          Homeobox genes)

         PAX 4,6                         Specify
        expression                    endocrine cell
                                         lineage

            Cells expressing
                                                       Cells expressing PAX 6
              PAX 4 & 6
                                                                 only
                                                                      α
 β Cells      δ Cells           γ Cells                           Cells
                                                              ( glucagon)
(Insulin)                      (Pancreatic
            (Somatostat        polypeptide)
Molecular Regulation of
        Kidney
     Development
Differentiation of the kidney involves interaction between the epithelium of
             Ureteric Bud & the mesenchyme of Metanephric Cap.

                                  FGF 2




                                   BMP
            Ureteric Bud            7                 Metanephric Cap
                            RE
                             T
                   MET




                                       GDNF
                         ( Glial Derived Neurotrophic Factor )

                                        HGF
                           ( Hepatocyte Growth Factor )

Thus, Signaling Pathway is established between these
Block Apoptosis

                                    Stimulate proliferation of
                                    Metanephric Cap

                       FGF           Maintain WT 1
                         2           production

                        BMP 7
            Ureteric                                 Metanephri
             Bud                          GDN          c Cap
                                            F
                                          HGF




Make the metanephric Cap competent to                   WT
 respond to induction by Ureteric Bud                    1

Stimulate growth        Regulate production
of Ureteric Bud          of GDNF & HGF
TO BE CONTINUED
      ISA …

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Molecular Embryology PART 1

  • 1. Molecular Embryology By: Dr. Khaled El Masry Assistant Lecturer of Human Anatomy & Embryology Mansoura Faculty of Medicine, Mansoura University, Mansoura , Egypt. 2013
  • 2. Molecular Regulation of Cardiac Development
  • 3. BMP 2, 4 + Inhibitors of WNT genes (In Endoderm & Lateral Plate Mesoderm ) Stimulate Production of Signals from Anterior Cranial Endoderm Expre ss NKX 2.5 Specify Cardiogenic Field in Overlying Mesoderm. Role in Cardiac Septation. Role in Conducting System Development. TBX-5 ( another Expressed later than NKX transcriptional factor) 2.5 contain T- Box. Role in Cardiac Septation
  • 4. Molecular Regulation of SomitE Differentiation
  • 5. Limb & body wall Epaxial muscles Activate Myogenin & MRF-5 muscles WNT proteins MYF-5 MYOD ( from Neural Tube) Myotubes & Myofibrils DM Midpart NT-3 (from Neural Tube) VM SHH Dermis D Scleroto me PAX 1 Initiate cascade of cartilage & bone forming genes Vertebral formation L BY: Interaction ( ) BMP-4 ( from lateral plate mesoderm) & WNT proteins ( from Dr. Khaled El Epidermis) WNT proteins PAX 3 Specify Dermomyotome Region of Somites Masry ( from Neural Tube)
  • 6. Molecular Regulation of Gut Development
  • 7. Differentiation of different regions of gut & its derivatives is dependent upon Reciprocal interaction ( ) Endoderm of GUT & Surrounding Splanchnic Mesoderm. SHH ( Expressed throughout gut endoderm) Induce expression HOX genes in Mesoderm Once expressed & Mesoderm specified by HOX genes Mesoderm instruct Endoderm to form various regions of Midgut & Hindgut Similar Interactions are responsible for Partitioning of Foregut.
  • 8. Molecular Regulation of LIVER Development
  • 9. All Foregut Endoderm has the ability to express liver-specific genes & to differentiate into Liver tissue But This expression is blocked by factors produced from surrounding tissues including: Ectoderm, non- cardiac mesoderm & Notochord. Liver Development occurs when: Cardiac Mesoderm FGF4 Block the inhibitory signals in prospective hepatic Region This process is partially Cells differentiate into regulated by HNF 3,4 hepatocytes & Biliary cell (Hepatocyte Nuclear lineage Transcription Factors 3 & 4 )
  • 10. Molecular Regulation of Pancreas Development
  • 11. Notochord FGF & Suppress SHH ( in Activin gut endoderm that form the will pancreas Upregulate PDX genes ( Pancreatic & Duodenal Homeobox genes) PAX 4,6 Specify expression endocrine cell lineage Cells expressing Cells expressing PAX 6 PAX 4 & 6 only α β Cells δ Cells γ Cells Cells ( glucagon) (Insulin) (Pancreatic (Somatostat polypeptide)
  • 12. Molecular Regulation of Kidney Development
  • 13. Differentiation of the kidney involves interaction between the epithelium of Ureteric Bud & the mesenchyme of Metanephric Cap. FGF 2 BMP Ureteric Bud 7 Metanephric Cap RE T MET GDNF ( Glial Derived Neurotrophic Factor ) HGF ( Hepatocyte Growth Factor ) Thus, Signaling Pathway is established between these
  • 14. Block Apoptosis Stimulate proliferation of Metanephric Cap FGF Maintain WT 1 2 production BMP 7 Ureteric Metanephri Bud GDN c Cap F HGF Make the metanephric Cap competent to WT respond to induction by Ureteric Bud 1 Stimulate growth Regulate production of Ureteric Bud of GDNF & HGF
  • 15. TO BE CONTINUED ISA …