Rose, M.F., Ahmad, K.A., Thaller, C. & Zoghbi, H.Y. Excitatory neurons of the proprioceptive, interoceptive, and arousal hindbrain networks share a developmental requirement for Math1. Proc. Natl. Acad. Sci. USA 106, 22462-22467

Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 12/2009; 106(52):22462-7. DOI: 10.1073/pnas.0911579106
Source: PubMed


Hindbrain networks important for sensation and arousal contain diverse neuronal populations with distinct projections, yet share specific characteristics such as neurotransmitter expression. The relationship between the function of these neurons, their developmental origin, and the timing of their migration remains unclear. Mice lacking the proneural transcription factor Math1 (Atoh1) lose neurons essential for hearing, balance, and unconscious proprioception. By using a new, inducible Math1(Cre*PR) allele, we found that Math1 is also required for the conscious proprioceptive system, including excitatory projection neurons of the dorsal column nuclei and for vital components of the interoceptive system, such as Barrington's nucleus, that is closely associated with arousal. In addition to specific networks, Math1 lineages shared specific neurotransmitter expression, including glutamate, acetylcholine, somatostatin, corticotropin releasing hormone, and nitric oxide. These findings identify twenty novel Math1 lineages and indicate that the Math1 network functions partly as an interface for conscious (early-born) and unconscious (late-born) proprioceptive inputs to the cortex and cerebellum, respectively. In addition, these data provide previously unsuspected genetic and developmental links between proprioception, interoception, hearing, and arousal.

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Available from: Matthew F. Rose, May 30, 2014
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    • "Potential functional divisions within the SOC GABAergic and glycinergic systems are less clear. This situation contrasts with the finding that all SOC glutamatergic neurons derive from the Atoh1 lineage (Maricich et al., 2009; Rose et al., 2009 ), and that expression of Atoh1 and Ptf1a parse cochlear nucleus neurons into glutamatergic and GABAergic/glycinergic populations (Hoshino et al., 2005). Given that Atoh1 and Ptf1a are both basic helix-loop-helix (bHLH) transcription factors, it is possible that an as yet unidentified bHLH protein lies upstream of En1 and plays a similar role in inhibitory SOC neurons. "
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    ABSTRACT: Little is known about the genetic pathways and transcription factors that control development and maturation of central auditory neurons. En1, a gene expressed by a subset of developing and mature superior olivary complex (SOC) cells, encodes a homeodomain transcription factor important for neuronal development in the midbrain, cerebellum, hindbrain and spinal cord. Using genetic fate-mapping techniques, we show that all En1-lineal cells in the SOC are neurons and that these neurons are glycinergic, cholinergic and GABAergic in neurotransmitter phenotype. En1 deletion does not interfere with specification or neural fate of these cells, but does cause aberrant positioning and subsequent death of all En1-lineal SOC neurons by early postnatal ages. En1-null cells also fail to express the transcription factor FoxP1, suggesting that FoxP1 lies downstream of En1. Our data define important roles for En1 in the development and maturation of a diverse group of brainstem auditory neurons.
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    • "The DNLL originates primarily in the isthmic Atoh1 + lineage (Wang et al. 2005; Rose et al. 2009; Machold and Fishell 2005) (Fig. 2). The INLL is derived from the alar plate of r1 (Moreno-Bravo et al. 2014) and the VNLL from r4 (Fig. 2) (Di Bonito et al. 2013b). "
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    • "Development (2014) 141, 4031-4041 doi:10.1242/dev.106559 DEVELOPMENT that migrate into ventral and isthmic r1 (Machold and Fishell, 2005; Wang et al., 2005; Green et al., 2014), contributing cells to multiple nuclei that form part of a wider hindbrain network of nuclei controlling proprioception, interoception and arousal (Rose et al., 2009). "
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    ABSTRACT: The cerebellum is a pre-eminent model for the study of neurogenesis and circuit assembly. Increasing interest in the cerebellum as a participant in higher cognitive processes and as a locus for a range of disorders and diseases make this simple yet elusive structure an important model in a number of fields. In recent years, our understanding of some of the more familiar aspects of cerebellar growth, such as its territorial allocation and the origin of its various cell types, has undergone major recalibration. Furthermore, owing to its stereotyped circuitry across a range of species, insights from a variety of species have contributed to an increasingly rich picture of how this system develops. Here, we review these recent advances and explore three distinct aspects of cerebellar development - allocation of the cerebellar anlage, the significance of transit amplification and the generation of neuronal diversity - each defined by distinct regulatory mechanisms and each with special significance for health and disease.
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