A complex genetic locus, polyhomeotic, is required for segmental specification and epidermal development in D....

Area of Science:

• Developmental biology
• Genetics
• Molecular biology

Background:

• The polyhomeotic (ph) gene is crucial for embryonic development.
• Null mutations in ph lead to embryonic lethality and loss of specific epidermal derivatives.
• Single-event mutations exhibit dominant gain-of-function phenotypes, similar to known developmental genes.

Purpose of the Study:

• To investigate the genetic complexity of the polyhomeotic (ph) locus.
• To understand the molecular basis of ph gene function and its unusual mutation requirements.
• To propose a model for the functional organization of the ph locus.

Main Methods:

• Positional cloning via chromosomal walk to localize the ph gene.
• Analysis of ph mutations resulting from DNA rearrangements.
• Hybridization studies to identify repetitive DNA elements in the ph region.

Main Results:

• The ph gene was localized using deficiencies and rearrangement-induced mutations.
• Two large, duplicated DNA sequences were identified within the ph locus.
• Lesions in either duplicated sequence disrupt ph gene function, confirming their importance.

Conclusions:

• The polyhomeotic (ph) locus is genetically complex, requiring two mutagenic events for a null phenotype.
• The presence of duplicated sequences is essential for normal ph gene function.
• A model is proposed to explain the unusual functional organization and genetic requirements of the ph locus.