Excitatory neurons of the proprioceptive, interoceptive, and arousal hindbrain networks share a developmental requirement for Math1

Abstract

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.auditory ͉ dorsal columns ͉ medial lemniscus ͉ proneural ͉ rhombic lip

Axonal Patterns and Targets of dA1 Interneurons in the Chick Hindbrain

“…Multiple studies provided essential knowledge regarding the role of Atoh1 in these processes (Marín and Puelles, 1995;Cambronero and Puelles, 2000;Bermingham et al, 2001;Machold and Fishell, 2005;Wang et al, 2005;Rose et al, 2009a). Here we combined genetic and morphological tools to follow the axonal patterns of chick dA1-interneurons, to decipher their targets and connections, and to investigate the role of the Lim-HD code in patterning dA1-axonal paths.…”

“…4 E-H ). As PCN neurons, as well as subsets of CN neurons, project to the cerebellum (Mason, 1986;Hatten and Heintz, 1995;Bermingham et al, 2001;Díaz et al, 2003;Doucet and Ryugo, 2003;Cicirata et al, 2005;Dipietrantonio and Dymecki, 2009;Rose et al, 2009a), we then wished to inspect the dA1 axonal routes in detail within the cerebellum. The cerebellum was dissected out from E9.5-E13.5 embryos and stained for the zinc finger transcription factor Zic1, which marks the EGL and IGL, and with the Ca 2ϩ -binding protein Calbindin, which marks the Purkinje layer, to delineate the various cerebellar domains (Baimbridge et al, 1992;Aruga et al, 1994Aruga et al, , 2002Grinberg et al, 2004).…”

Development of the cerebellum: simple steps to make a ‘little brain’

“…A key clarifying concept was identification of the origins of granule cell precursors at the rhombic lip, a thin strip of neuroepithelium that borders the non-neuronal roof plate of the fourth ventricle (Alder et al, 1996;Wingate, 2001). Although it spans the entire rhombencephalon, contributing to a variety of distinct auditory, proprioceptive and interoceptive hindbrain circuits (Rodriguez and Dymecki, 2000;Landsberg et al, 2005;Maricich et al, 2009;Rose et al, 2009), the rhombic lip of the cerebellar anlage (rhombomere 1) is the exclusive source of granule cell precursors that then migrate tangentially to form the EGL (Wingate and Hatten, 1999). The cells in the rhombic lip that contribute to the EGL already express Atoh1, which is induced by TGFβ signals secreted from the neighbouring Box 4.…”

Electroporation of the Hindbrain to Trace Axonal Trajectories and Synaptic Targets in the Chick Embryo

“…It regulates basic functions including respiration, consciousness, hearing, and motor coordination [1][2][3] . During early embryonic development, the vertebrate hindbrain is transiently subdivided along its anterior-posterior (AP) axis into repetitive rhombomeres, in which distinct neuronal cell types are formed and generate multiple brainstem nuclei centers 4 .…”