Central nervous system distribution of the transcription factor Phox2b in the adult rat

Abstract

Phox2b is required for development of the peripheral autonomic nervous system and a subset of cranial nerves and lower brainstem nuclei. Phox2b mutations in man cause diffuse autonomic dysfunction and deficits in the automatic control of breathing. Here we study the distribution of Phox2b in the adult rat hindbrain to determine whether this protein is selectively expressed by neurons involved in respiratory and autonomic control. In the medulla oblongata, Phox2b-immunoreactive nuclei were present in the dorsal vagal complex, intermediate reticular nucleus, dorsomedial spinal trigeminal nucleus, nucleus ambiguus, catecholaminergic neurons, and retrotrapezoid nucleus (RTN). Phox2b was expressed by both central excitatory relays of the sympathetic baroreflex (nucleus of the solitary tract and C1 neurons) but not by the inhibitory relay of this reflex. Phox2b was absent from the ventral respiratory column (VRC) caudal to RTN and rare within the parabrachial nuclei. In the pons, Phox2b was confined to cholinergic efferent neurons (salivary, vestibulocochlear) and noncholinergic peritrigeminal neurons. Rostral to the pons, Phox2b was detected only in the oculomotor complex. In adult rats, Phox2b is neither a comprehensive nor a selective marker of hindbrain autonomic pathways. This marker identifies a subset of hindbrain neurons that control orofacial movements (dorsomedial spinal trigeminal nucleus, pontine peritrigeminal neurons), balance and auditory function (vestibulocochlear efferents), the eyes, and both divisions of the autonomic efferent system. Phox2b is virtually absent from the respiratory rhythm and pattern generator (VRC and dorsolateral pons) but is highly expressed by neurons involved in the chemical drive and reflex regulation of this oscillator.

CO2-Sensitive Preinspiratory Neurons of the Parafacial Respiratory Group Express Phox2b in the Neonatal Rat

“…jneurosci.org as supplemental material). The general pattern was basically identical to that of adult rat, whereas expression in the facial nucleus was absent in adult rat (Stornetta et al, 2006;Kang et al, 2007). Phox2b-expressing cells in the parafacial region of the rostral medulla are implicated in sensing CO 2 to affect respiratory rhythm generation in adult rat (Stornetta et al, 2006).…”

“…Phox2b-expressing cells are distributed in several regions of the hindbrain involved in the autonomic nervous system in embryonic, neonatal, and adult rodents (Dauger et al, 2003;Kang et al, 2007). Heterozygous mutations of PHOX2B in the form of polyalanine expansions or frameshifts cause congenital central hypoventilation syndrome (CCHS) and late-onset CHS (LO-CHS), symptoms of which manifest in adulthood (Amiel et al, 2003;Blanchi and Sieweke, 2005;Weese-Mayer et al, 2005).…”

Breathing withPhox2b

“…noradrenergic nuclei A6 and A5; Hilaire et al 2004) while others are not (e.g. the parabrachial and Kö lliker-Fuse nuclei; Kang et al 2007;J.-F. Brunet, unpublished data).…”

Genetic identification of a hindbrain nucleus essential for innate vocalization

“…Inhibitory neurons associated with the NTS and area postrema are not derived from dA3, but emerge from dB neurons (18). A1/C1 and A2/C2 adrenergic groups express tyrosine hydroxylase, but again some neurons down-regulate Phox2b and vGlut2 in postnatal life (19,20). Changes in the generation of dA3 neuronal derivatives were quantified in Olig3 and Tlx3 mutant mice.…”