Lbx1 Acts as a Selector Gene in the Fate Determination of Somatosensory and Viscerosensory Relay Neurons in the Hindbrain

Sieber, Martin; Storm, Robert; Martı́nez-de-la-Torre, Margaret; Müller, Thomas; Wende, Hagen; Reuter, Katja; Vasyutina, Elena; Birchmeier, Carmen

doi:10.1523/jneurosci.0717-07.2007

Cited by 119 publications

(212 citation statements)

References 38 publications

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“…Thus, throughout cranial ganglia and dA neurons, Brn3a expression, and the attendant somatic identity, appear as a ground state on which Phox2b superimposes a visceral identity in dA3 interneurons and epibranchial ganglia. A reverse switch was reported in dB3 and dBLb interneurons, normally destined to a somatic fate (trigeminal sensory nuclei) (11,25), upon inactivation of the homeobox gene Lbx1 that results in up-regulation of Phox2b and contribution to a visceral fate (nTS) (11). Thus, Lbx1 imposes a somatic identity by repressing Phox2b expression and the attendant visceral identity.…”

Section: Discussionmentioning

confidence: 97%

“…In the PNS, Tlx3, Drg11, and Islet1 are expressed in all sensory ganglia, visceral and somatic (14,20,30, and this work). In the CNS, Tlx3, Drg11, and Lmx1b are expressed in the precursors of the nTS (9,20,22), spinal and principal trigeminal nuclei (11,20,31,32), spinal dorsal horn interneurons (20,23,33). The expression of these transcription factors is neither strictly specific for sensory neurons [e.g., Tlx3 is expressed in sympathetic ganglia (14) and Lmx1b in serotonergic neurons (34)] nor inclusive of all sensory neurons, but largely biased toward them.…”

Section: Discussionmentioning

confidence: 99%

“…In the hindbrain, relay sensory neurons of the nTS are born from E9.5 to E13.5 (10) in the domain of dA3 progenitors, which extends from rhombomere (r) 4 to r7 (11,12) and switch on Phox2b postmitotically (9). In homozygous Phox2b null embryos, nTS precursors switch on Lmx1b and Rnx/Tlx3 and start migrating ventrally (9)-as they do in heterozygous or wild-type embryos (9,12).…”

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Homeoprotein Phox2b commands a somatic-to-visceral switch in cranial sensory pathways

D’Autréaux

Coppola

Hirsch

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

111

123

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Taste and most sensory inputs required for the feedback regulation of digestive, respiratory, and cardiovascular organs are conveyed to the central nervous system by so-called "visceral" sensory neurons located in three cranial ganglia (geniculate, petrosal, and nodose) and integrated in the hindbrain by relay sensory neurons located in the nucleus of the solitary tract. Visceral sensory ganglia and the nucleus of the solitary tract all depend for their formation on the pan-visceral homeodomain transcription factor Phox2b, also required in efferent neurons to the viscera. We show here, by genetically tracing Phox2b + cells, that in the absence of the protein, many visceral sensory neurons (first-and second-order) survive. However, they adopt a fate-including molecular signature, cell positions, and axonal projections-akin to that of somatic sensory neurons (first-and second-order), located in the trigeminal, superior, and jugular ganglia and the trigeminal sensory nuclei, that convey touch and pain sensation from the orofacial region. Thus, the cranial sensory pathways, somatic and visceral, are related, and Phox2b serves as a developmental switch from the former to the latter.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Homeoprotein Phox2b commands a somatic-to-visceral switch in cranial sensory pathways

D’Autréaux

Coppola

Hirsch

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

111

123

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“…In vertebrates terminal selector genes have been studied mostly in the context of lineage restriction and forward neuronal differentiation, but their subsequent role in maintaining neuronal subtype identity is largely unknown. For example, constitutive germ-line deletion of Tlx1/3, Helt, Lbx1, and Sox6 resulted in the acquisition by the relevant cell lineages of alternative default cell fates (24)(25)(26)(27)(28). However, the potential plasticity of the neuronal identities promoted by these transcription factors has not been addressed.…”

Section: Discussionmentioning

confidence: 99%

Transcription factor LIM homeobox 7 (Lhx7) maintains subtype identity of cholinergic interneurons in the mammalian striatum

Lopes

Wijk

Neves

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The generation and maintenance of a plethora of neuronal subtypes is essential for normal brain function. Nevertheless, little is known about the molecular mechanisms that maintain the defining characteristics of neurons following their initial postmitotic specification. Using conditional gene ablation in mice, we demonstrate here that the homeodomain protein LIM homeobox (Lhx)7 is essential for maintaining the morphological and molecular characteristics of cholinergic interneurons of the striatum. Lhx7-depleted cholinergic interneurons extinguish expression of several subtype-specific markers, including choline acetyl transferase and Isl1, and are respecified into Lhx6-expressing mature GABAergic interneurons. Additional expression studies support a model where Lhx7 controls the choice between cholinergic or GABAergic identity by gating a cross inhibitory regulation between Isl1 and Lhx6. By demonstrating that the switch between alternative striatal interneuron fates depends on persistent activity of a single transcription factor, we provide evidence that the intrinsic plasticity of mammalian forebrain neuronal subtypes is maintained after the initial specification and lineage commitment and possibly throughout life.neuronal subtype specification | medial ganglionic eminence-derived interneurons T he information-processing ability of the nervous system depends on the formation of functional neuronal circuits composed of a highly heterogeneous population of neurons. Recent progress has identified molecular cascades that control the generation of distinct neuronal subtypes during development (1-3) but the mechanisms that maintain the identity of neurons following lineage commitment and differentiation are currently unclear. Identifying such mechanisms is critical for understanding phenotypic plasticity in the nervous system and, ultimately, influencing its ability to adjust during normal development, disease, or injury.The striatum is a subcortical structure that integrates multiple inputs from the cortex, thalamus, and midbrain and relays information to the output domains of the basal ganglia via its principal population of projection neurons (4, 5). Balanced striatal output, which is critical for motor and cognitive activity, depends on local circuits controlled by distinct subpopulations of GABAergic and cholinergic interneurons (5). Both GABAergic and cholinergic striatal interneurons (GSIs and CSIs, respectively) are derived from Nkx2.1-expressing progenitors of the medial ganglionic eminence (MGE) (6, 7), which, upon exit from the cell cycle, express the LIM homeodomain (LIM HD) transcription factors LIM homeobox 6 (Lhx6) and LIM homeobox 7 (Lhx7) (8). A subset of these precursors maintains expression of Lhx6 and differentiate into mature GABAergic interneurons expressing the neuropeptide somatostatin (Sst) or the calcium-binding protein parvalbumin (Pv) (9, 10). The remaining precursors induce expression of the LIM HD protein Isl1, down-regulate Lhx6, and differentiate into CSIs (8). In adult animals, all ...

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“…1A-D;Sieber et al, 2007). Some of these populations, such as dA4 and dB1, extend through rh2-7, while others, such as dA3, are present only in some rhombomeres (Sieber et al, 2007;Storm et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Loss ofPtf1aLeads to a Widespread Cell-Fate Misspecification in the Brainstem, Affecting the Development of Somatosensory and Viscerosensory Nuclei

Iskusnykh¹,

Steshina²,

Chizhikov

2016

J. Neurosci.

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The brainstem contains diverse neuronal populations that regulate a wide range of processes vital to the organism. Proper cell-fate specification decisions are critical to achieve neuronal diversity in the CNS, but the mechanisms regulating cell-fate specification in the developing brainstem are poorly understood. Previously, it has been shown that basic helix-loop-helix transcription factor Ptf1a is required for the differentiation and survival of neurons of the inferior olivary and cochlear brainstem nuclei, which contribute to motor coordination and sound processing, respectively. In this study, we show that the loss of Ptf1a compromises the development of the nucleus of the solitary tract, which processes viscerosensory information, and the spinal and principal trigeminal nuclei, which integrate somatosensory information of the face. Combining genetic fate-mapping, birth-dating, and gene expression studies, we found that at least a subset of brainstem abnormalities in Ptf1a Ϫ/Ϫ mice are mediated by a dramatic cell-fate misspecification in rhombomeres 2-7, which results in the production of supernumerary viscerosensory and somatosensory neurons of the Lmx1b lineage at the expense of Pax2 ϩ GABAergic viscerosensory and somatosensory neurons, and inferior olivary neurons. Our data identify Ptf1a as a major regulator of cell-fate specification decisions in the developing brainstem, and as a previously unrecognized developmental regulator of both viscerosensory and somatosensory brainstem nuclei.

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Lbx1 Acts as a Selector Gene in the Fate Determination of Somatosensory and Viscerosensory Relay Neurons in the Hindbrain

Cited by 119 publications

References 38 publications

Homeoprotein Phox2b commands a somatic-to-visceral switch in cranial sensory pathways

Homeoprotein Phox2b commands a somatic-to-visceral switch in cranial sensory pathways

Transcription factor LIM homeobox 7 (Lhx7) maintains subtype identity of cholinergic interneurons in the mammalian striatum

Loss ofPtf1aLeads to a Widespread Cell-Fate Misspecification in the Brainstem, Affecting the Development of Somatosensory and Viscerosensory Nuclei

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