Abstract/Details

The long-range regulation of Hoxa13 in the developing limbs and genital bud


2007 2007

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Abstract (summary)

The posterior HoxA and HoxD homeodomain transcription factor genes are essential for appendicular development. My thesis research demonstrates that a domain of genes upstream of Hoxa13 (Evx1, Hibadh, Tax1bp1, and Jazf1) are embryonically co-expressed in the distal limb and genital bud during embryogenesis (E11.5–E13.5), suggesting the existence of a common/shared enhancer element influencing their expression. A similar co-expressed gene neighborhood exists at the ancestrally related HoxD locus. Paralogous sequence comparison of 1 Mb genomic DNA upstream of the HoxA and HoxD clusters revealed five highly conserved non-coding sequences. Two of these sequences are clustered within homologously conserved sequences on each chromosome: mmA13CNS, ∼2.25 kb located within the fourth intron of Hibadh upstream of Hoxa13, and mmD13CNS, ∼4 kb located within the previously identified 'distal limb enhancer' critical region upstream of Hoxd13. To test mmA13CNS function, this element was placed in cis with a minimal promoter and shown to be insufficient for precise Hoxa13-like expression in the limb buds or genital bud of LacZ transgenic mice, even though non- Hoxa13-like LacZ expression was reproducibly found in these tissues.

Subsequently, this research demonstrated the sufficiency of a single critical region for mouse Hoxa13-like embryonic genital bud expression, as assayed by β-globin minimal promoter LacZ recombinant BAC transgenes. This research also shows that at least two sequences remote to the HoxA cluster are collectively sufficient to drive expression in the developing distal limbs, similar in timing and domains to the endogenous Hoxa13 expression pattern.

Indexing (details)


Subject
Molecular biology;
Genetics
Classification
0307: Molecular biology
0369: Genetics
Identifier / keyword
Biological sciences, Developing limbs, Genital bud, Hoxa13
Title
The long-range regulation of Hoxa13 in the developing limbs and genital bud
Author
Lehoczky, Jessica A.
Number of pages
187
Publication year
2007
Degree date
2007
School code
0127
Source
DAI-B 68/08, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9780549175452
Advisor
Innis, Jeffrey W.
University/institution
University of Michigan
University location
United States -- Michigan
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3276229
ProQuest document ID
304849514
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/304849514
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