Active Suppression of Interneuron Programs within Developing Motor Neurons Revealed by Analysis of Homeodomain Factor HB9 (original) (raw)

et al., 1997), Nkx2.2 (Briscoe et al., 1999), and members † Laboratory of Immunoregulation of the Gli family (Hui et al., 1994). Specifically, Nkx2.2 ϩ National Institute of Allergy progenitors appear to produce dorsal exiting MNs (d-MNs) and Infectious Diseases and a class of ventral interneurons (V3), whereas Pax6 ϩ National Institutes of Health progenitors give rise to ventral projecting MNs (v-MNs) Bethesda, Maryland 20892 and a number of distinct interneuron types (V1, V2) (Ericson et al., 1997; Sharma et al., 1998). In an analogous fashion, the dorsal neural tube is patterned by tumor Summary growth factor ␤ (TGF␤) family molecules, including the bone morphogenetic proteins (BMPs) and activin, that Sonic hedgehog (Shh) specifies the identity of both initiate the specification of dorsal neuronal classes (Lee motor neurons (MNs) and interneurons with morphoet al., 1998). gen-like activity. Here, we present evidence that the Many of the transcription factors marking MN and homeodomain factor HB9 is critical for distinguishing interneuron classes have been suspected to control cell MN and interneuron identity in the mouse. Presumpfate specification, yet most are encountered in multiple tive MN progenitors and postmitotic MNs express cell types, including both interneurons and MNs (Tanabe HB9, whereas interneurons never express this factor. and Jessell, 1996; Pfaff and Kintner, 1998). For example, This pattern resembles a composite of the avian hothe LIM-HD factors Lhx3/4, known to promote the v-MN mologs MNR2 and HB9. In mice lacking Hb9, the gecell fate, are present in precursors for both v-MNs and netic profile of MNs is significantly altered, particularly V2 interneurons (Sharma et al., 1998) and can drive exby upregulation of Chx10, a gene normally restricted pression of the V2 gene Chx10 in ectopic contexts (Tanto a class of ventral interneurons. This aberrant gene abe et al., 1998). Thus, it is unclear how an MN utilizes expression is accompanied by topological disorganithese factors to establish its identity while avoiding the zation of motor columns, loss of the phrenic and abduinterneuron characteristics they might confer. More gencens nerves, and intercostal nerve pathfinding defects.