BMPs direct sensory interneuron identity in the developing spinal cord using signal-specific not morphogenic activities.

Madeline G Andrews,Eliana Ochoa-Bolton,Lorenzo M Del Castillo,Ken Yamauchi,Jan Smogorzewski,Samantha J Butler

doi:10.7554/elife.30647

Madeline G Andrews, Eliana Ochoa-Bolton + Show 4 more

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https://doi.org/10.7554/elife.30647

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Abstract

The Bone Morphogenetic Protein (BMP) family reiteratively signals to direct disparate cellular fates throughout embryogenesis. In the developing dorsal spinal cord, multiple BMPs are required to specify sensory interneurons (INs). Previous studies suggested that the BMPs act as concentration-dependent morphogens to direct IN identity, analogous to the manner in which sonic hedgehog patterns the ventral spinal cord. However, it remains unresolved how multiple BMPs would cooperate to establish a unified morphogen gradient. Our studies support an alternative model: BMPs have signal-specific activities directing particular IN fates. Using chicken and mouse models, we show that the identity, not concentration, of the BMP ligand directs distinct dorsal identities. Individual BMPs promote progenitor patterning or neuronal differentiation by their activation of different type I BMP receptors and distinct modulations of the cell cycle. Together, this study shows that a 'mix and match' code of BMP signaling results in distinct classes of sensory INs.

Highlights

A common theme in organ development is the existence of signaling centers: restricted sources of inductive growth factors that pattern the identity of surrounding tissues
Multiple Bone Morphogenetic Protein (BMP) are present in the dorsal spinal cord (Lee et al, 1998; Liem et al, 1997), and BMP signaling has been shown to be critical for dorsal spinal identity (Hazen et al, 2012; WineLee et al, 2004)
We further evaluated the effect of BMPs on cell cycle dynamics, by assessing these cell cycle markers in mouse embryonic stem cell (mESC) treated with BMP4, BMP5, BMP6, BMP7 or GDF7

Summary

Introduction

A common theme in organ development is the existence of signaling centers: restricted sources of inductive growth factors that pattern the identity of surrounding tissues. More recent studies have suggested that Shh acts as a temporal morphogen, such that progenitor identity depends on the duration of exposure to Shh (Kong et al, 2015; Dessaud et al, 2010). Together, these studies have been highly influential, both demonstrating that Shh functions as a textbook example of a morphogen and providing a general mechanism by which inductive signaling centers may specify an array of cellular fates

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