Limits...
LIM homeobox protein 5 (Lhx5) is essential for mamillary body development.

Miquelajáuregui A, Sandoval-Schaefer T, Martínez-Armenta M, Pérez-Martínez L, Cárabez A, Zhao Y, Heide M, Alvarez-Bolado G, Varela-Echavarría A - Front Neuroanat (2015)

Bottom Line: Here we demonstrate that Lhx5, a LIM-HD domain transcription factor expressed early in the developing posterior hypothalamus, is required for the generation of the MM and its derived tracts.The MM markers Foxb1, Sim2, and Lhx1 are absent in Lhx5 knock-out mice from early embryonic stages, suggesting abnormal specification of this region.Interestingly, we also found an ectopic domain expressing Lhx2 and Lhx9 along the anterio-posterior hypothalamic axis.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México Querétaro, Mexico.

ABSTRACT
The mamillary body (MM) is a group of hypothalamic nuclei related to memory and spatial navigation that interconnects hippocampal, thalamic, and tegmental regions. Here we demonstrate that Lhx5, a LIM-HD domain transcription factor expressed early in the developing posterior hypothalamus, is required for the generation of the MM and its derived tracts. The MM markers Foxb1, Sim2, and Lhx1 are absent in Lhx5 knock-out mice from early embryonic stages, suggesting abnormal specification of this region. This was supported by the absence of Nkx2.1 and expansion of Shh in the prospective mamillary area. Interestingly, we also found an ectopic domain expressing Lhx2 and Lhx9 along the anterio-posterior hypothalamic axis. Our results suggest that Lhx5 controls early aspects of hypothalamic development by regulating gene expression and cellular specification in the prospective MM.

No MeSH data available.


Related in: MedlinePlus

MM is absent in Lhx5 mutants. (A,B) Nissl staining in sagittal sections of control mice at E18.5 reveals the MM (arrowhead) that appears absent in Lhx5 mutants. (C,D) Comparable sections processed for Sevier–Munger silver staining reveal the fx (empty arrow), pm (filled arrow), mtt, (empty arrowhead), and mteg (filled arrowhead) tracts, in control but not in mutant littermates (anterior is to the left). (E–H)In situ hybridization for Foxb1 and Lhx1 in E18.5 coronal sections stained the MM in controls (arrowhead) and showed no expression in Lhx5 mutants. Note the presence of Lhx1 expression in the ZI (white arrow). Abbreviations: fx, fornix; MM, mamillary; mteg, mammillotegmental; mtt, mammillothalamic; PG, pontine gray; pm, principal mamillary; ZI, zona incerta. Scale bar: 400 μm.
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Figure 2: MM is absent in Lhx5 mutants. (A,B) Nissl staining in sagittal sections of control mice at E18.5 reveals the MM (arrowhead) that appears absent in Lhx5 mutants. (C,D) Comparable sections processed for Sevier–Munger silver staining reveal the fx (empty arrow), pm (filled arrow), mtt, (empty arrowhead), and mteg (filled arrowhead) tracts, in control but not in mutant littermates (anterior is to the left). (E–H)In situ hybridization for Foxb1 and Lhx1 in E18.5 coronal sections stained the MM in controls (arrowhead) and showed no expression in Lhx5 mutants. Note the presence of Lhx1 expression in the ZI (white arrow). Abbreviations: fx, fornix; MM, mamillary; mteg, mammillotegmental; mtt, mammillothalamic; PG, pontine gray; pm, principal mamillary; ZI, zona incerta. Scale bar: 400 μm.

Mentions: To determine the role of Lhx5 in the development of the MM, we analyzed knock-out mice lacking Lhx5 function (Zhao et al., 1999). Since absence of Lhx5 leads to perinatal lethality, potentially caused by breathing-control deficiencies associated with early hindbrain specification (Sheng et al., 1997; Cepeda-Nieto et al., 2005), we performed histological analyses on E18.5 embryos, when the development of the MM and its main axonal tracts is complete (Alvarez-Bolado et al., 2000; Marion et al., 2005), (Figure 2).


LIM homeobox protein 5 (Lhx5) is essential for mamillary body development.

Miquelajáuregui A, Sandoval-Schaefer T, Martínez-Armenta M, Pérez-Martínez L, Cárabez A, Zhao Y, Heide M, Alvarez-Bolado G, Varela-Echavarría A - Front Neuroanat (2015)

MM is absent in Lhx5 mutants. (A,B) Nissl staining in sagittal sections of control mice at E18.5 reveals the MM (arrowhead) that appears absent in Lhx5 mutants. (C,D) Comparable sections processed for Sevier–Munger silver staining reveal the fx (empty arrow), pm (filled arrow), mtt, (empty arrowhead), and mteg (filled arrowhead) tracts, in control but not in mutant littermates (anterior is to the left). (E–H)In situ hybridization for Foxb1 and Lhx1 in E18.5 coronal sections stained the MM in controls (arrowhead) and showed no expression in Lhx5 mutants. Note the presence of Lhx1 expression in the ZI (white arrow). Abbreviations: fx, fornix; MM, mamillary; mteg, mammillotegmental; mtt, mammillothalamic; PG, pontine gray; pm, principal mamillary; ZI, zona incerta. Scale bar: 400 μm.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4621302&req=5

Figure 2: MM is absent in Lhx5 mutants. (A,B) Nissl staining in sagittal sections of control mice at E18.5 reveals the MM (arrowhead) that appears absent in Lhx5 mutants. (C,D) Comparable sections processed for Sevier–Munger silver staining reveal the fx (empty arrow), pm (filled arrow), mtt, (empty arrowhead), and mteg (filled arrowhead) tracts, in control but not in mutant littermates (anterior is to the left). (E–H)In situ hybridization for Foxb1 and Lhx1 in E18.5 coronal sections stained the MM in controls (arrowhead) and showed no expression in Lhx5 mutants. Note the presence of Lhx1 expression in the ZI (white arrow). Abbreviations: fx, fornix; MM, mamillary; mteg, mammillotegmental; mtt, mammillothalamic; PG, pontine gray; pm, principal mamillary; ZI, zona incerta. Scale bar: 400 μm.
Mentions: To determine the role of Lhx5 in the development of the MM, we analyzed knock-out mice lacking Lhx5 function (Zhao et al., 1999). Since absence of Lhx5 leads to perinatal lethality, potentially caused by breathing-control deficiencies associated with early hindbrain specification (Sheng et al., 1997; Cepeda-Nieto et al., 2005), we performed histological analyses on E18.5 embryos, when the development of the MM and its main axonal tracts is complete (Alvarez-Bolado et al., 2000; Marion et al., 2005), (Figure 2).

Bottom Line: Here we demonstrate that Lhx5, a LIM-HD domain transcription factor expressed early in the developing posterior hypothalamus, is required for the generation of the MM and its derived tracts.The MM markers Foxb1, Sim2, and Lhx1 are absent in Lhx5 knock-out mice from early embryonic stages, suggesting abnormal specification of this region.Interestingly, we also found an ectopic domain expressing Lhx2 and Lhx9 along the anterio-posterior hypothalamic axis.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México Querétaro, Mexico.

ABSTRACT
The mamillary body (MM) is a group of hypothalamic nuclei related to memory and spatial navigation that interconnects hippocampal, thalamic, and tegmental regions. Here we demonstrate that Lhx5, a LIM-HD domain transcription factor expressed early in the developing posterior hypothalamus, is required for the generation of the MM and its derived tracts. The MM markers Foxb1, Sim2, and Lhx1 are absent in Lhx5 knock-out mice from early embryonic stages, suggesting abnormal specification of this region. This was supported by the absence of Nkx2.1 and expansion of Shh in the prospective mamillary area. Interestingly, we also found an ectopic domain expressing Lhx2 and Lhx9 along the anterio-posterior hypothalamic axis. Our results suggest that Lhx5 controls early aspects of hypothalamic development by regulating gene expression and cellular specification in the prospective MM.

No MeSH data available.


Related in: MedlinePlus