Transcription Factor Hb9 Is Expressed in Glial Cell Lineages in the Developing Mouse Spinal Cord

Author:

Letchuman Sunjay,Tucker Ashley,Miranda Diego,Adkins Robert L.ORCID,Aceves Miriam,Dietz Valerie,Jagrit Vipin,Leonards Amy,Lee Young il,Dulin Jennifer N.

Abstract

AbstractHb9 (Mnx1) is a transcription factor described as a spinal cord motor neuron (MN)-specific marker and critical factor for the postmitotic specification of these cells. To date, expression of Hb9 in other cell types has not been reported. We performed a fate-mapping approach to examine distributions of Hb9-expressing cells and their progeny (“Hb9-lineage cells”) within the embryonic and adult spinal cord of Hb9cre;Ai14 mice. We found that Hb9-lineage cells are distributed in a gradient of increasing abundance throughout the rostrocaudal spinal cord axis during embryonic and postnatal stages. Furthermore, although the majority of Hb9-lineage cells at cervical spinal cord levels are MNs, at more caudal levels, Hb9-lineage cells include small-diameter dorsal horn neurons, astrocytes, and oligodendrocytes. In the peripheral nervous system, we observed a similar phenomenon with more abundant Hb9-lineage Schwann cells in muscles of the lower body versus upper body muscles. We cultured spinal cord progenitorsin vitroand found that gliogenesis was increased by treatment with the caudalizing factor FGF-8B, while glial tdTomato expression was increased by treatment with both FGF-8B and GDF-11. Together, these observations suggest that early and transient expression of Hb9 in spinal cord neural progenitors may be induced by caudalizing factors such as FGF and GDF signaling. Furthermore, our work raises the possibility that early Hb9 expression may influence the development of spinal cord macroglia and Schwann cells, especially at caudal regions. Together, these findings highlight the importance of using caution when designing experiments using Hb9cremice to perform spinal cord MN-specific manipulations.

Funder

HHS | NIH | National Institute of Neurological Disorders and Stroke

Craig H. Neilsen Foundation

TIRR Foundation

Paralyzed Veterans of America Research Foundation

Wings for Life

Publisher

Society for Neuroscience

Subject

General Medicine,General Neuroscience

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