Transcription factors define the neuroanatomical organization of the medullary reticular formation

Abstract

The medullary reticular formation contains large populations of inadequately described, excitatory interneurons that have been implicated in multiple homeostatic behaviors including breathing, viserosensory processing, vascular tone, and pain. Many hindbrain nuclei show a highly stereotyped pattern of localization across vertebrates suggesting a strong underlying genetic organization. Whether this is true for neurons within the reticular regions of hindbrain is unknown. Hindbrain neurons are derived from distinct developmental progenitor domains each of which expresses distinct patterns of transcription factors (TFs). These neuronal populations have distinct characteristics such as transmitter identity, migration, and connectivity suggesting developmentally expressed TFs might identify unique subpopulations of neurons within the reticular formation. A fate-mapping strategy using perinatal expression of reporter genes within Atoh1, Dbx1, Lmx1b, and Ptf1a transgenic mice coupled with immunohistochemistry (IHC) and in situ hybridization (ISH) were used to address the developmental organization of a large subset of reticular formation glutamatergic neurons. All hindbrain lineages have relatively large populations that extend the entire length of the hindbrain. Importantly, the location of neurons within each lineage was highly constrained. Lmx1b- and Dbx1- derived populations were both present in partially overlapping stripes within the reticular formation extending from dorsal to ventral brain. Within each lineage, distinct patterns of gene expression and organization were localized to specific hindbrain regions. Rostro-caudally sub-populations differ sequentially corresponding to proposed pseudo-rhombomereic boundaries. Dorsal-ventrally, sub-populations correspond to specific migratory positions. Together these data suggests the reticular formation is organized by a highly stereotyped developmental logic.

How the brainstem controls orofacial behaviors comprised of rhythmic actions

“…Modern genetic and circuit analysis tools will be crucial to the above studies. Evidence of particular groups of neurons with specific circuit functions is likely to come from studies in which molecularly- defined cell populations in the medulla 121 can be targeted and manipulated in vivo . Such manipulations have already proven invaluable in parsing other motor circuits in the spinal cord 122–124 .…”

Central pattern generator for vocalization: is there a vertebrate morphotype?

“…The premotor neurons patterning the activity of these neuromuscular units may share developmental origins from neurotransmitter and transcription factor-defined hindbrain populations comparable to those recently identified in mammals [45] and zebrafish [46,47] (also see Sweeney and Kelley, this issue). These neurons, in turn, may have distinct intrinsic and/or network properties like those being identified in fish and frogs [10,20,23,29] that determine the vocal system’s enhanced temporal precision and synchrony [10,20,48] compared, for example, to motoneuron activity underlying locomotion [e.g., 11,20,49].…”

Diving into the mammalian swamp of respiratory rhythm generation with the bullfrog

“…Rhombomere 7/8 gives rise to pharyngeal arch 4 and the vagus nerve, providing critical innervation of the larynx and glottis (Guthrie, 2007;Straka et al, 2006). The same rhombomere contains the preBötC in mammals (Champagnat and Fortin, 1997;Gray, 2013). Could it be that the inspiratory oscillator of mammals, the preBötC, evolved from the water-breathing oscillator of fish?…”