Term
| Primitive streak and gastrulation |
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Definition
| FGF8 downregulates E-cadherin and upregulates Brachury. This promotes invagination of primitive streak cells to form the endoderm and mesoderm. |
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Term
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Definition
| Cells from anterior visceral mesoderm (AVE) produce LIM1, OTX2 and HESX1 along with cerebus and lefty which all inhibit Nodal and induce head formation. |
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Term
| Maintainance of primitive streak |
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Definition
| FGF8 induces surrounding cells to produce Nodal, which maintain the primitive streak. Nodal is responsible for the induction of dorsalization and ventralization of mesoderm. |
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Term
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Definition
| BMP4 and FGF expressed throughout the mesoderm induce formation of intermediate and lateral mesoderm. The primitive streak produces chordin, noggin and follistatin in the midline that induces notochord and paraxial mesoderm formation. |
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Term
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Definition
5HT on the left induces FGF8 that induces Nodal and Lefty2. These induce PITX2, which regulates lefthandedness.
Lefty1 acts as a barrier from left signals to cross to the right from the floor of the neural tube.
Shh is eventually expressed only on the right.
MAO degrades 5HT on the right.
Snail regulates right side genes. |
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Term
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Definition
BMP4 and FGF induces ectoderm to differentiate into epidermis.
Inhibition of BMP4 by chordin, noggin and follistatin in the midline induces neurulation of the ectoderm. |
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Term
| Neural plate borders and axes |
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Definition
| Cranial border regulated by retinoic acid, Caudal plate induced by Wnt3a and FGF. Floor induced by Shh from notochord. BMP4 and FGF regulate lateral borders of neural plate by producing PAX3. |
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Term
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Definition
| PAX3 induces Snail and FOXD3 that specify cells as neural crest and Slug which promotes cell migration. |
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Term
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Definition
Noggin and SHH from the notochord and neural tube floor causes the neural tube to produce a factor that induces PAX1 production by the ventral somite that induces sclerotome formation.
Wnt from the dorsal neural tube activate PAX3 to form the dermomyotome.
Wnt alone causes the medial part of the dermomyotome to produce MYF5, leading to back muscle formation.
Neurotrophin-3 produced from the dorsal neural tube induces middle part of dermomyotome to become dermis.
Wnt inhibited by BMP4 from the lateral plate mesoderm induce lateral dermomyotome to produce MYOD, which induces limb and trunk muscles. |
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Term
| Lung-mesenchyme interaction |
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Definition
Mesenchyme produces FGF10, induces budding.
FGF10 induces production of Shh at the apex of the bud.
Shh inhibits action of FGF10 at the apex of the bud, causing the bud to branch. |
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Term
| Regional specification of the gut |
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Definition
| Craniocaudal gradient of retinoic acid, increasing caudally (unlike within a single somite). |
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Term
| Epithelial-mesenchyme interactions in the gut |
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Definition
Shh expression in the gut endoderm upregulates specific Hox genes in the mesoderm. This specifies the mesoderm, which then instructs the endoderm to form various components.
Evidence comes from knockout mice studies. |
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Term
| Transcription factors for oesophagus and stomach |
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Definition
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Term
| Transcription factors for pancreas and duodenum |
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Definition
| PDX1 and Pft1a plus PAX1 and PAX6 for endocrine components of pancreas |
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Term
| Transcription factors for small bowel |
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Definition
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Term
| Transcription factors for large bowel |
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Definition
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Term
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Definition
| BMP from the septum transversum and FGF2 from the heart relieve the inhibition of surrounding tissues on HNF3 and HNF4, allowing liver differentiation. |
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Term
| Induction of mesenchyme for metanephric development |
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Definition
Mesenchyme express WT1 which makes it responsive to inductive signals from the ureteric bud.
The ureteric buds stimulate proliferation of the mesenchyme through FGF2 and BMP7, continuing to promote WT1. |
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Term
| Induction of branching and growth of ureteric bud |
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Definition
WT1 induces production of glial-derived neurotrophic factor (GDNF) and hepatocyte growth factor (HGF) by the mesenchyme.
The ureteric bud epithelium express RTKs for GDNF and HNF, called RET and MET. |
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Term
| Conversion of the metanephric mesenchyme to epithelium |
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Definition
| Ureteric bud expresses Wnt9B and Wnt6 which upregulate PAX2 and Wnt4 in the metanephric mesenchyme. PAX2 causes condensation of the mesenchyme and WNT4 causes the mesenchyme to epithelialize. |
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Term
| Induction of testis formation |
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Definition
| SRY gene on Y chromosome produces the testis-determining factor which induces the formation of testis cords from the primitive sex cords. |
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Term
| Male genital duct development |
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Definition
SRY and/or SOX9 induce FGF9 that causes the tubules of the mesonephric duct to penetrate the gonadal ridge.
SRY and/or SOX9 upregulate Steroidogenesis Factor 1 (SF1) which stimulates the differentiation of Sertoli (to produce AMH) and Leydig cells (to produce testosterone).
Testosterone enters target tissues and either remains intact or is converted to dihydrotestosterone by 5-a-reductase.
Testosterone induces virilisation of the mesonephric ducts to form the vas deferens, seminal vesicles, efferent ductules and epididymis.
Dihydrotestosterone induce differentiation of the male external genitalia. |
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Term
| Female genital duct development |
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Definition
WNT4 is the ovary-determining gene, which induces DAX1, which inhibits SOX9.
Wnt4 induces oestrogens which induce the paramesonephric ducts to form the uterine tubes, uterus, cervix and upper vagina.
Oestrogens also form the female external genitalia. |
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Term
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Definition
Craniocaudal axis regulated by Hox genes via Retinoic acid (transplantation of thoracic somite at the neck causes a cervical rib).
'Segmentation clock' = Cyclic expression of Nodal and Wnt lead to oscillating signalling molecule concentrations. Borders are determined by opposing gradients: Retinoic acid maximum cranially, FGF and Wnt3a maximum caudally. |
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Term
| Holt-Oram Syndrome causative mutation |
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Definition
| TBX5 gene - Involved in forelimb development and atrial septation. HOS will manifest as an ASD and foreshortening of the upper limb. |
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Term
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Definition
| Lateral plate mesoderm induce limb outgrowth formation by secreting TBX4 and FGF10 in the hindlimb and TBX5 and FGF10. |
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Term
| Proximodistal axis of limb development |
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Definition
Dorsal ectodermal cells express Radical fringe, which induces SER2 expression. Ventral ectodermal cells express Engrailed-1 which repressed Racidal fringe. The Apical Ectodermal Ridge occurs at the border of these two regions.
AER induces FGF4 and FGF8, which maintain the mesenchymal progress zone proximal to the AER. |
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Term
Anteroposterior axis of limb development
(thumb-little finger) |
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Definition
Zone of polarizing activity (ZPA) is a cluster of cells at the posterior border of the limb near the body wall. It moves distalward to remain close to the AER as the limb grows.
It secretes Retinoic Acid that upregulates Shh, which regulates the AP axis.
If RA or SHH are misexpressed, a mirror image duplication of limb structures occurs. |
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Term
| Dorsoventral axis of limb development |
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Definition
| The ventral ectoderm expresses BMPs, which induce EN1, which represses Wnt7a, limiting it to the dorsal ectoderm. Wnt7a induces LMX1. Wnt7a also maintains Shh expression in the ZPA and thus indirectly influences anteroposterior axis. |
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Term
| Skeletogenesis patterning |
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Definition
HOXA and HOXD clusters, induced by combinatorial expression of FGFs, Shh and Hox genes.
Hoxd13 mutations lead to polydactyly and fused digits.
Hoxa13 result in reduced size of A and P digits. |
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Term
| Meromelia (partial absence of a limb) - Phocomelia (due to thalidomide) |
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Definition
| Thalidomide arrested growth at the progess zone and prolonged exposure to FGF4 anf FGF8, thus inducing differentiation into hand structures. |
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Term
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Definition
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Term
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Definition
BMP type signalling proteins (GDF5, BMP4)
Mutations in GDF5 lead to Chondrodysplasias. (Shortening of bones, loss of joints)
Joints are formed at joint interzone - cartilaginous condensations where the joint is sculpted by apoptosis under the regulation of Wnt14.
Ossification then influenced by GH, thyroid hormones and IFG1. FGF3 inhibits growth
Activating mutation in FGF3R leads to dwarfism. |
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