Multiple sources of Shh are critical for the generation and scaling of ventral spinal cord oligodendrocyte precursor populations.

Abstract

Graded Sonic Hedgehog (Shh) signaling emanating from notochord and floorplate patterns the early neural tube. Soon thereafter, Shh signaling strength within the ventricular zone becomes dis-contiguous and discontinuous along the ventral to dorsal axis suggesting a distribution of Shh that cannot be achieved by diffusion alone. Here we discover that sequential activation of Shh expression by ventricular zone derivatives is critical for counteracting a precocious exhaustion of the Olig2 precursor cell population of the pMN domain at the end of motor neuron genesis and during the subsequent phase of ventral oligodendrocyte precursor production. Selective expression of Shh by motor neurons of the lateral motor column at the beginning of oligodendrogenesis ensures a more yielding pMN domain at limb levels compared to thoracic levels. Thus, patterned expression of Shh by ventricular zone derivatives including earlier born neurons contributes to the scaling of the spinal cord along the anterior - posterior axis by regulating the activity of a select ventricular zone precursor domain at later stages of development.