[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Embryology](https://durgical.com/en/embryology/) › [General embryology: weeks 1 to 8](https://durgical.com/en/embryology/#a-general) › Molecular regulation: Shh, Wnt, FGF, BMP, Hox genes and retinoic acid

[Embryology](https://durgical.com/en/embryology/) · [General embryology: weeks 1 to 8](https://durgical.com/en/embryology/#a-general)

# Molecular regulation: Shh, Wnt, FGF, BMP, Hox genes and retinoic acid

- Topic

A handful of chemical signals tells each embryonic cell where it is and what to become.

Updated 2026-11-01

**See it in 3D:** [Spinal cord](https://durgical.com/en/anatomy/spinal-cord/) · [Lens](https://durgical.com/en/anatomy/lens/)

## Key points

- SHH: ventral and posterior (ZPA); failure → holoprosencephaly.
- FGF from the apical ectodermal ridge: proximal–distal limb growth.
- Wnt: dorsal; BMP: epidermis and dorsal; blocking it → neural plate.
- Hox: cranial–caudal identity; regulated by retinoic acid.
- Isotretinoin = excess retinoic acid = severe embryopathy.

## What it is

Development uses a few signaling pathways over and over in different organs. Molecules such as Sonic hedgehog (SHH), Wnt, FGF and BMP act as concentration-dependent signals: cells near the source receive more and take a different fate from distant ones. Hox genes, regulated partly by retinoic acid, give each segment of the cranial–caudal axis its identity. Knowing them explains genetic malformations and the effect of teratogens such as isotretinoin.

## Key facts

- SHH: notochord and floor plate (ventral neural tube, sclerotome), the limb's zone of polarizing activity (little finger to thumb axis), forebrain midline.
- Wnt: dorsal neural tube and somite, primitive streak, dorsal limb (WNT7A).
- FGF: the limb's apical ectodermal ridge (proximal–distal growth, FGF8), primitive streak, bone growth (FGFR3).
- BMP (TGF-β family): makes ectoderm into epidermis; blocking it with noggin and chordin gives neural plate; roof plate of the neural tube.
- Hox genes: expressed in the same order along the chromosome and along the body (colinearity); retinoic acid regulates them.
- Sidedness: NODAL, LEFTY and PITX2 on the left.

## Developmental signals and what happens when they fail

| Signal | Where it acts | Too little or too much |
| --- | --- | --- |
| SHH | Notochord, ventral neural tube, limb ZPA | Holoprosencephaly, cyclopia; polydactyly if excess |
| Wnt | Dorsal neural tube and limb | Limb and axis defects |
| FGF | Apical ectodermal ridge, bone | Achondroplasia (FGFR3), craniosynostosis (FGFR2) |
| BMP | Epidermis, dorsal neural tube | Skeletal and neural induction defects |
| Hox | Identity of cranial–caudal segments | Synpolydactyly (HOXD13), hand-foot-genital (HOXA13) |
| Retinoic acid | Regulates Hox, hindbrain, arches | Excess (isotretinoin): craniofacial, heart and CNS defects |

## Markers

- SHH
- WNT
- FGF8
- BMP4
- HOX
- Retinoic acid
- NODAL
- TBX5
- PAX6

## Clinical notes

- SHH mutations: the commonest genetic cause of nonsyndromic holoprosencephaly.
- Achondroplasia: an activating FGFR3 mutation that brakes growth-plate cartilage.
- Isotretinoin in pregnancy: excess retinoic acid that disturbs Hox expression (ears, heart, thymus, nervous system).
- Transcription factors: TBX5 (Holt–Oram: arm and heart), PAX6 (aniridia), PAX3 (Waardenburg), SRY (testis).
- Cyclopamine, a plant alkaloid that blocks SHH signaling, caused cyclopia in lambs: a classic pathway teratogen.

## Memory aid

To find your way in the embryo: SHH points to the 'floor' and the little finger, Wnt to the 'roof', FGF to the growing 'tip', and Hox genes put the 'floor number' on each segment.

## Test yourself

Think of the answer, then tap the question to see it.

## Which signal does the limb's zone of polarizing activity make, and which axis does it set?

Sonic hedgehog (SHH); it sets the anterior–posterior axis, thumb to little finger.

## Which apical ectodermal ridge signal keeps the limb growing?

FGF (mainly FGF8), which drives proximal–distal growth.

## Why is isotretinoin teratogenic?

It is a retinoid: excess retinoic acid disturbs Hox gene expression and damages the face, ear, heart, thymus and nervous system.

## Which brain malformation is linked to SHH mutations?

Holoprosencephaly: the forebrain fails to split into two hemispheres.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/embryology/molecular-regulation-shh-wnt-fgf-bmp-hox-genes-and-retinoic-acid/)

## See it in 3D

The structures of Durgical's 3D anatomy where it is found.

- [Spinal cord](https://durgical.com/en/anatomy/spinal-cord/)
- [Lens](https://durgical.com/en/anatomy/lens/)

## Related

- [Week 3: gastrulation and the trilaminar disc](https://durgical.com/en/embryology/week-3-gastrulation-and-the-trilaminar-disc/)
- [Primitive streak and notochord (nucleus pulposus, sacrococcygeal teratoma)](https://durgical.com/en/embryology/primitive-streak-and-notochord/)
- [Neurulation and closure of the neural tube](https://durgical.com/en/embryology/neurulation-and-closure-of-the-neural-tube/)
- [Paraxial mesoderm and somites: sclerotome, myotome, dermatome](https://durgical.com/en/embryology/paraxial-mesoderm-and-somites-sclerotome-myotome-dermatome/)
- [Limb development: the apical ectodermal ridge, ZPA and limb rotation](https://durgical.com/en/embryology/limb-development-the-apical-ectodermal-ridge-zpa-and-limb-rotation/)
- [Holoprosencephaly](https://durgical.com/en/embryology/holoprosencephaly/)
- [Achondroplasia (FGFR3)](https://durgical.com/en/embryology/achondroplasia/)
- [Isotretinoin and other retinoids](https://durgical.com/en/embryology/isotretinoin-and-other-retinoids/)
- [Craniosynostosis](https://durgical.com/en/embryology/craniosynostosis/)
- [Sex determination: SRY, anti-Müllerian hormone and testosterone](https://durgical.com/en/embryology/sex-determination-sry-anti-mullerian-hormone-and-testosterone/)

[← All of embryology](https://durgical.com/en/embryology/)

Educational content on embryonic development; not a guide to prenatal diagnosis or to medicines in pregnancy and no substitute for a health professional's advice. No doses are given.

Sources: Langman's Medical Embryology, 13th ed., ch. 1: Introduction to Molecular Regulation and Signaling (Wolters Kluwer, 2015); [SHH gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/shh/) (MedlinePlus (U.S. National Library of Medicine), 2026); [Waardenburg syndrome: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/waardenburg-syndrome/) (MedlinePlus (U.S. National Library of Medicine), 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/embryology/molecular-regulation-shh-wnt-fgf-bmp-hox-genes-and-retinoic-acid/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/embryology/molecular-regulation-shh-wnt-fgf-bmp-hox-genes-and-retinoic-acid/