scholarly journals 09-P076 A rhombomere 4-derived auditory circuitry is dependent on Hoxb1 function

2009 ◽  
Vol 126 ◽  
pp. S173
Author(s):  
Maria Di Bonito ◽  
Marta Mancuso ◽  
Gennaro Andolfi ◽  
Anna Maria Franzé ◽  
Luigi Sequino ◽  
...  
Keyword(s):  
Development ◽  
2002 ◽  
Vol 129 (16) ◽  
pp. 3825-3837 ◽  
Author(s):  
Lisa Maves ◽  
William Jackman ◽  
Charles B. Kimmel

The segmentation of the vertebrate hindbrain into rhombomeres is highly conserved, but how early hindbrain patterning is established is not well understood. We show that rhombomere 4 (r4) functions as an early-differentiating signaling center in the zebrafish hindbrain. Time-lapse analyses of zebrafish hindbrain development show that r4 forms first and hindbrain neuronal differentiation occurs first in r4. Two signaling molecules, FGF3 and FGF8, which are both expressed early in r4, are together required for the development of rhombomeres adjacent to r4, particularly r5 and r6. Transplantation of r4 cells can induce expression of r5/r6 markers, as can misexpression of either FGF3 or FGF8. Genetic mosaic analyses also support a role for FGF signaling acting from r4. Taken together, our findings demonstrate a crucial role for FGF-mediated inter-rhombomere signaling in promoting early hindbrain patterning and underscore the significance of organizing centers in patterning the vertebrate neural plate.


Development ◽  
2002 ◽  
Vol 129 (10) ◽  
pp. 2339-2354 ◽  
Author(s):  
James M. McClintock ◽  
Mazen A. Kheirbek ◽  
Victoria E. Prince

We have used a morpholino-based knockdown approach to investigate the functions of a pair of zebrafish Hox gene duplicates, hoxb1a and hoxb1b, which are expressed during development of the hindbrain. We find that the zebrafish hoxb1 duplicates have equivalent functions to mouse Hoxb1 and its paralogue Hoxa1. Thus, we have revealed a ‘function shuffling’ among genes of paralogue group 1 during the evolution of vertebrates. Like mouse Hoxb1, zebrafish hoxb1a is required for migration of the VIIth cranial nerve branchiomotor neurons from their point of origin in hindbrain rhombomere 4 towards the posterior. By contrast, zebrafish hoxb1b, like mouse Hoxa1, is required for proper segmental organization of rhombomere 4 and the posterior hindbrain. Double knockdown experiments demonstrate that the zebrafish hoxb1 duplicates have partially redundant functions. However, using an RNA rescue approach, we reveal that these duplicated genes do not have interchangeable biochemical functions: only hoxb1a can properly pattern the VIIth cranial nerve. Despite this difference in protein function, we provide evidence that the hoxb1 duplicate genes were initially maintained in the genome because of complementary degenerative mutations in defined cis-regulatory elements.


2008 ◽  
Vol 36 (10) ◽  
pp. 3214-3225 ◽  
Author(s):  
Xavier Lampe ◽  
Omar Abdel Samad ◽  
Allan Guiguen ◽  
Christelle Matis ◽  
Sophie Remacle ◽  
...  

Development ◽  
2001 ◽  
Vol 128 (8) ◽  
pp. 1299-1312 ◽  
Author(s):  
N. Vlachakis ◽  
S.K. Choe ◽  
C.G. Sagerstrom

Many Hox proteins are thought to require Pbx and Meis co-factors to specify cell identity during embryogenesis. Here we demonstrate that Meis3 synergizes with Pbx4 and Hoxb1b in promoting hindbrain fates in the zebrafish. We find that Hoxb1b and Pbx4 act together to induce ectopic hoxb1a expression in rhombomere 2 of the hindbrain. In contrast, Hoxb1b and Pbx4 acting together with Meis3 induce hoxb1a, hoxb2, krox20 and valentino expression rostrally and cause extensive transformation of forebrain and midbrain fates to hindbrain fates, including differentiation of excess rhombomere 4-specific Mauthner neurons. This synergistic effect requires that Hoxb1b and Meis3 have intact Pbx-interaction domains, suggesting that their in vivo activity is dependent on binding to Pbx4. In the case of Meis3, binding to Pbx4 is also required for nuclear access. Our results are consistent with Hoxb1b and Meis3 interacting with Pbx4 to form complexes that regulate hindbrain development during zebrafish embryogenesis.


Development ◽  
1993 ◽  
Vol 118 (2) ◽  
pp. 527-538 ◽  
Author(s):  
S. Guthrie ◽  
V. Prince ◽  
A. Lumsden

During hindbrain development, cells become segregated into segmental groups, rhombomeres, by mechanisms that are presently unknown. One contributory factor early in development may be an alternating periodicity in cell surface properties down the neuraxis. This possibility was previously suggested by experiments in which tissue from different segmental levels was apposed in the absence of a boundary. New boundaries were regenerated only when rhombomeres from adjacent positions or positions three rhombomeres distant from one another were apposed. Combinations of two odd-numbered or two even-numbered rhombomeres usually failed to generate a boundary. In order to pursue this phenomenon to the cellular level, we have used two approaches, both involving donor-to-host transplantation. First, quail rhombomeres were grafted at various hindbrain levels of a chick host. Apposition of rhombomere 4 (r4) with r3 was concomitant with negligible cell mixing across the interface. By contrast, combinations of r3 with r5 or with r3 tissue led to cell mixing that was more extensive in combinations of identical rhombomeres (r3 with r3) than between two alternate ones (r3 with r5). Secondly, we grafted small pieces of fluorescently prelabelled chick rhombomere tissue at various hindbrain levels of chick hosts. In most cases, cells dispersed widely when transplanted orthopically or two segments distant from that of their origin. Cells transplanted into an adjacent segment, however, showed a tendency to remain undispersed. Among the different graft combinations, furthermore, there was a variation in the extent of dispersal that showed an additional level of complexity not revealed in boundary regeneration experiments. The possibility is raised that the early partitioning of rhombomeres involves a hierarchy in the adhesive preferences of cell-cell interactions along the neuraxis.


Development ◽  
1999 ◽  
Vol 126 (23) ◽  
pp. 5523-5531 ◽  
Author(s):  
I. Pata ◽  
M. Studer ◽  
J.H. van Doorninck ◽  
J. Briscoe ◽  
S. Kuuse ◽  
...  

In this paper, we show that the transcription factor GATA3 is dynamically expressed during hindbrain development. Function of GATA3 in ventral rhombomere (r) 4 is dependent on functional GATA2, which in turn is under the control of Hoxb1. In particular, the absence of Hoxb1 results in the loss of GATA2 expression in r4 and the absence of GATA2 results in the loss of GATA3 expression. The lack of GATA3 expression in r4 inhibits the projection of contralateral vestibuloacoustic efferent neurons and the migration of facial branchiomotor neurons similar to Hoxb1-deficient mice. Ubiquitous expression of Hoxb1 in the hindbrain induces ectopic expression of GATA2 and GATA3 in ventral r2 and r3. These findings demonstrate that GATA2 and GATA3 lie downstream of Hoxb1 and provide the first example of Hox pathway transcription factors within a defined population of vertebrate motor neurons.


Development ◽  
1995 ◽  
Vol 121 (4) ◽  
pp. 957-974 ◽  
Author(s):  
M. Frasch ◽  
X. Chen ◽  
T. Lufkin

The HOM-C/Hox complexes are an evolutionary related family of genes that have been shown to direct region-specific development of the animal body plan. We examined in transgenic mice the DNA regulatory elements that determine the temporal and spatially restricted expression of two of the earliest and most anteriorly expressed murine genes, Hoxa-1 and Hoxa-2, which are homologues of the labial and proboscipedia genes of Drosophila. In both mouse and Drosophila, these genes have been shown to play a critical role in head development. We identified three independent enhancers which direct distinct portions of the Hoxa-1 and Hoxa-2 expression domains during early murine embryogenesis. Two enhancers mediate hindbrain-specific expression, being active in either rhombomere 2, the most anterior rhombomere expressing Hoxa-2, or in rhombomere 4, a region where Hoxa-1 and Hoxa-2 have been shown to exert critical developmental roles. The third enhancer is essential for the most extensive expression domain of Hoxa-1 and contains a retinoic acid response element. Point mutations within the retinoic acid response element abolish expression in neuroepithelium caudal to rhombomere 4, supporting a natural role for endogenous retinoids in patterning of the hindbrain and spinal cord. Analysis of the murine Hoxa-2 rhombomere 2-specific enhancer in Drosophila embryos revealed a distinct expression domain within the arthropod head segments, which parallels the expression domain of the Hoxa-2 homologue proboscipedia. These results suggest an evolutionary conservation between HOM-C/Hox family members, which includes a conservation of certain DNA regulatory elements and possible regulatory cascades.


2017 ◽  
Vol 222 (8) ◽  
pp. 3509-3542 ◽  
Author(s):  
Maria Di Bonito ◽  
Michèle Studer ◽  
Luis Puelles

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