title: Distinct roles of Hoxa2 and Krox20 in the development of rhythmic neural networks controlling inspiratory depth, respiratory frequency, and jaw opening.
abstract: BACKGROUND
  Little is known about the involvement of molecular determinants of segmental patterning of rhombomeres (r) in the development of rhythmic neural networks in the mouse hindbrain. Here, we compare the phenotypes of mice carrying targeted inactivations of Hoxa2, the only Hox gene expressed up to r2, and of Krox20, expressed in r3 and r5. We investigated the impact of such mutations on the neural circuits controlling jaw opening and breathing in newborn mice, compatible with Hoxa2-dependent trigeminal defects and direct regulation of Hoxa2 by Krox20 in r3.
  
  
  RESULTS
  We found that Hoxa2 mutants displayed an impaired oro-buccal reflex, similarly to Krox20 mutants. In contrast, while Krox20 is required for the development of the rhythm-promoting parafacial respiratory group (pFRG) modulating respiratory frequency, Hoxa2 inactivation did not affect neonatal breathing frequency. Instead, we found that Hoxa2-/- but not Krox20-/- mutation leads to the elimination of a transient control of the inspiratory amplitude normally occurring during the first hours following birth. Tracing of r2-specific progenies of Hoxa2 expressing cells indicated that the control of inspiratory activity resides in rostral pontine areas and required an intact r2-derived territory.
  
  
  CONCLUSIONS
  Thus, inspiratory shaping and respiratory frequency are under the control of distinct Hox-dependent segmental cues in the mammalian brain. Moreover, these data point to the importance of rhombomere-specific genetic control in the development of modular neural networks in the mammalian hindbrain.
authors: NGI, UPR 2216, Institut de Neurobiologie Alfred Fessard IFR2218, Centre National de Recherche Scientifique, F-91198 Gif sur Yvette Cedex, France. Fabrice.Chatonnet@ens-lyon.org
authors: Fabrice
authors: F
authors: Chatonnet
authors: Ludovic J
authors: LJ
authors: Wrobel
authors: Valérie
authors: V
authors: Mézières
authors: Massimo
authors: M
authors: Pasqualetti
authors: Sébastien
authors: S
authors: Ducret
authors: Emmanuel
authors: E
authors: Taillebourg
authors: Patrick
authors: P
authors: Charnay
authors: Filippo M
authors: FM
authors: Rijli
authors: Jean
authors: J
authors: Champagnat
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019521:Body Patterning / Q000235:genetics; D051767:Early Growth Response Protein 2 / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D007568:Jaw / Q000294:innervation / Q000502:physiology*; D008410:Masticatory Muscles / Q000254:growth & development / Q000294:innervation; D051379:Mice; D018345:Mice, Knockout; D009415:Nerve Net / Q000254:growth & development* / Q000378:metabolism; D010507:Periodicity; D012125:Respiratory Center / Q000254:growth & development* / Q000378:metabolism; D012143:Respiratory Physiological Phenomena; D012249:Rhombencephalon / Q000254:growth & development* / Q000378:metabolism; D014276:Trigeminal Nerve / Q000254:growth & development / Q000378:metabolism
chemical_list: D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D018398:Homeodomain Proteins; C489833:Hoxa2 protein, mouse