Biomedical subjects

R P Kühnlein

Publications and source records attributed to R P Kühnlein.

8 recordsLinked to original sources

PubMed2000

Ectopic Sox3 activity elicits sensory placode formation.

The induction of sensory organ placodes, in particular the lens placode, represents the paradigm for induction. We show that medaka Sox3 is expressed in the neuroectoderm and in the placodes of all sensory organs prior to placode formation and subsequently in placode-derived tissues. Ectopic Sox3 expression leads to ectopic expression of Pax6 and Eya1 in embryonic ectoderm and causes ectopic lens and otic vesicle formation. The descendants of cells ectopically expressing Sox3-mRNA contribute to ectopic lens tissue. This suggests a permissive role for Sox3 in establishing a placodal competence. In addition, ectopic Sox3 expression leads to the dysgenesis of the endogenous sensory organs. Both effects of ectopic Sox3 expression can be separated by ectopic expression of a truncated Sox3 variant depending on its expression level. Our data suggests that Sox3 is a permissive factor for sensory placode formation and plays an important role in sensory organ development.

Amino Acid Sequence↗

PubMed1998

A transcription unit at the ken and barbie gene locus encodes a novel Drosophila zinc finger protein.

We describe a novel Drosophila transcription unit, located in chromosome region 60A. It encodes a zinc finger protein that is expressed in distinct spatial and temporal patterns during embryogenesis. Its initial expression occurs in a stripe at the anterior and the posterior trunk boundary, respectively. The two stripes are activated and spatially controlled by gap-gene activities. The P-element of the enhancer trap line l(2)02970 is inserted in the 5'-region of the transcript and causes a ken and barbie (ken) phenotype, associated with malformation of male genital structures.

Amino Acid Sequence↗

PubMed1998

The transcription factors KNIRPS and KNIRPS RELATED control cell migration and branch morphogenesis during Drosophila tracheal development.

Cell migration during embryonic tracheal system development in Drosophila requires DPP and EGF signaling to generate the archetypal branching pattern. We show that two genes encoding the transcription factors KNIRPS and KNIRPS RELATED possess multiple and redundant functions during tracheal development. knirps/knirps related activity is necessary to mediate DPP signaling which is required for tracheal cell migration and formation of the dorsal and ventral branches. Ectopic knirps or knirps related expression in lateral tracheal cells respecifies their anteroposterior to a dorsoventral migration behavior, similar to that observed in the case of ectopic DPP expression. In dorsal tracheal cells knirps/knirps related activity represses the transcription factor SPALT; this repression is essential for secondary and terminal branch formation. However, in cells of the dorsal trunk, spalt expression is required for normal anteroposterior cell migration and morphogenesis. spalt expression is maintained by the EGF receptor pathway and, hence, some of the opposing activities of the EGF and DPP signaling pathways are mediated by spalt and knirps/knirps related. Furthermore, we provide evidence that the border between cells acquiring dorsal branch and dorsal trunk identity is established by the direct interaction of KNIRPS with a spalt cis-regulatory element.

Animals↗

PubMed1997

Regulation of Drosophila spalt gene expression.

The region-specific homeotic gene spalt is involved in the specification of terminal versus trunk structures during early Drosophila embryogenesis. Later in development spalt activity participates in specific processes during organogenesis and larval imaginal disc development. The multiple functions of spalt are reflected in distinct spatio-temporal expression patterns throughout development. Here we show that spalt cis-regulatory sequences for region-specific and organ-specific expression are clustered. Their organization may provide the structural basis for the diversification of expression pattern within the spalt/spalt related/spalt adjacent gene complex. We also examined the transacting factor requirement for the blastodermal spalt expression domains. They are under the genetic control of maternal and gap gene products and we show that these products are able to bind to corresponding spalt cis-acting sequences in vitro. The results suggest that the transacting factors, as defined by genetic studies, functionally interact with the spalt regulatory region. In addition, we provide evidence that a zygotic gene product of the terminal system, Tailless, cooperates with the maternal gene product Caudal and thereby activates gene expression in the terminal region of the embryo.

Animals↗

PubMed1996

Isolation, characterization, and organ-specific expression of two novel human zinc finger genes related to the Drosophila gene spalt.

The region-specific homeotic gene spalt (sal) of Drosophila specifies head and tail as opposed to trunk segments. During later stages of ontogenesis, sal is also expressed and required in a small number of tissues and organs in the developing embryo. sal encodes a zinc finger protein of unusual but characteristic structure. We made use of these unique features to isolate sal-like genes from humans. Here we report the isolation and molecular characterization of two sal-like transcription units, termed Hsal1 and Hsal2, which are located on chromosomes 16q12.1 and 14q11.1-q12.1, respectively. Their transcripts are expressed in a limited number of adult organs, including the brain. While Hsal2 is evenly expressed in different brain areas, Hsal1 transcripts preferentially accumulate in the corpus callosum and the substantia nigra. In the fetal brain, transcripts of both genes were detected in neurons. The arrangement of sal-like zinc finger domains and their high degree of sequence similarity suggest a novel and conserved subfamily of human zinc finger transcription factors that is closely related to the Drosophila gene product encoded by the gene sal.

Adult↗

PubMed1996

Regulation, function and potential origin of the Drosophila gene spalt adjacent, which encodes a secreted protein expressed in the early embryo.

During early embryogenesis of Drosophila the spatial and temporal expression patterns of the region-specific homeotic gene spalt (sal) and the neighbouring gene spalt adjacent (sala) extensively overlap. We show that the initial expression patterns of the two genes in the blastoderm also have identical genetic controls. However, while sal encodes a transcription factor, sala encodes a precursor protein from which a functional signal peptide is cleaved off to generate the secreted sala protein. Ectopic expression or absence of sala protein does not affect embryonic development, adult viability or fertility. In addition to sal and sala, we identified a third gene nearby, termed spalt related (salr), which shares coding sequence similarity and a late embryonic expression pattern with sal, but lacks the early expression domains that are shared by sal and sala. These results suggest that the three genes and their present cis-regulatory regions arose through a chromosomal rearrangement involving local duplication and transposition events in the 32F/33A region on the left arm of the second chromosome.

Amino Acid Sequence↗

PubMed1996

Dual function of the region-specific homeotic gene spalt during Drosophila tracheal system development.

We report that the region-specific homeotic gene spalt affects the Drosophila tracheal system at two different stages of embryonic development. Both lack-of-function and gain-of-function experiments show that blastodermal spalt activity restricts tracheal development to 10 bilaterally positioned pairs of tracheal placodes in the trunk region by repressing placode formation in parasegments 2, 3 and 14. The results suggest that the activity of the zinc-finger type transcription factor encoded by spalt suppresses the molecular pathway that establishes tracheal development. spalt function is also necessary for the directed migration of the dorsal trunk cells, a distinct subset of tracheal cells. This process is a prerequisite for the formation of the dorsal trunk generated by fusion of adjacent tracheal metameres into a common tubular structure. The directed cell migration, in which spalt gene function participates, seems to be independent of branch fusion and general tracheal cell migration processes.

Animals↗

PubMed1994

spalt encodes an evolutionarily conserved zinc finger protein of novel structure which provides homeotic gene function in the head and tail region of the Drosophila embryo.

The region specific homeotic gene spalt (sal) of Drosophila melanogaster promotes the specification of terminal pattern elements as opposed to segments in the trunk. Our results show that the previously reported sal transcription unit was misidentified. Based on P-element mediated germ line transformation and DNA sequence analysis of sal mutant alleles, we identified the transcription unit that carries sal function. sal is located close to the misidentified transcription unit, and it is expressed in similar temporal and spatial patterns during embryogenesis. The sal gene encodes a zinc finger protein of novel structure composed of three widely spaced 'double zinc finger' motifs of internally conserved sequences and a single zinc finger motif of different sequence. Antibodies produced against the sal protein show that sal is first expressed at the blastoderm stage and later in restricted areas of the embryonic nervous system as well as in the developing trachea. The antibodies detect sal homologous proteins in corresponding spatial and temporal patterns in the embryos of related insect species. Sequence analysis of the sal gene of Drosophila virilis, a species which is phylogenetically separated by approximately 60 million years, suggests that the sal function is conserved during evolution, consistent with its proposed role in head formation during arthropod evolution.

Amino Acid Sequence↗