Painting the Nervous System with Gradients
A newly formed neural tube looks uniform, but its future is anything but. Along its length and height, chemical signals create invisible gradients that tell cells what to become. The nervous system is literally patterned by diffusion.
Dorsal–Ventral: From Sensory to Motor
On the ventral (belly) side, a central player is the notochord, a midline rod beneath the neural tube. It releases sonic hedgehog (Shh), a signaling molecule that turns the ventral neural tube into a well-organized series of progenitor domains.
Shh first induces Shh expression in the floor plate, the tube’s ventral-most region. From there, it diffuses outward. Cells interpret Shh by concentration:
- Low Shh → ventral interneurons
- Higher Shh → motor neurons
- Highest Shh → floor plate cells themselves
Here, Shh acts as a morphogen—a molecule whose level determines cell fate. It signals by binding Patched1, releasing the brake on Smoothened and activating Gli transcription factors (GLI1, GLI2, GLI3), which reprogram gene expression. Disruption of Shh signaling can cause severe malformations like holoprosencephaly, where the forebrain fails to split properly.
On the dorsal (back) side, signals come from BMPs produced by the overlying epidermal ectoderm. These pattern the dorsal neural tube, promoting sensory interneuron fates by altering SMAD transcription factor activity.
Head–Tail: Forebrain to Spinal Cord
Along the rostrocaudal (anteroposterior) axis, other cues dominate. In the hindbrain and spinal cord, FGF and retinoic acid help assign positional identities. Hox genes, arranged in ordered clusters on DNA, turn on in overlapping domains: 3′ end genes respond to retinoic acid in the hindbrain, whereas 5′ end genes activate more caudally in the spinal cord.
For example, Hoxb-1 expression in rhombomere 4 is crucial for forming the facial nerve. Without it, neurons instead resemble those of the trigeminal nerve, a striking demonstration of how a single patterning gene can redirect identity.
The Takeaway
By reading gradients of Shh, BMPs, retinoic acid and Hox activity, the neural tube converts smooth space into a mosaic of distinct neuron types. The brain’s complex map begins as a chemical landscape.